Different Phases Of Bipolar Disorder Research Articles

Latent Profile Analysis of Suicidal Ideation in Chinese Individuals with Bipolar Disorder.

Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.

Echocardiographic evaluation of myocardial strain in bipolar disorder across different phases: A comparative study with healthy controls.

This study aims to investigate the relationship between different phases of bipolar disorder (depressive, manic, and euthymic) and myocardial deformation, assessed by echocardiography, compared to healthy controls. It seeks to elucidate whether these phases of bipolar disorder are associated with different myocardial strain patterns, thus contributing to the understanding of cardiovascular implications in bipolar disorder. A cross-sectional design was employed at Dursun Odabaş Medical Centre, Psychiatry Clinic of Van Yüzüncü Yl University. The study enrolled 200 participants, divided into 4 groups: 50 in a depressive phase, 50 in a manic phase, 50 in an euthymic phase of bipolar disorder, and 50 healthy volunteers. Participants underwent detailed electrocardiographic and ECG evaluations, focusing on myocardial strain patterns and cardiac function. Statistical analyses, including ANOVA and chi-square tests, were used to compare the groups. Significant differences in global longitudinal strain (GLS) values were observed between the groups. The manic phase group exhibited the highest GLS (21.51), followed by the euthymic (20.75), depressive (20.25), and healthy control groups (19.0). The E/A ratio of the mitral valve also varied, with the manic group displaying the highest ratio (1.21). Other echocardiographic parameters such as left atria size and Ejection Fraction also differed significantly between the groups. The study concluded that the phases of bipolar disorder are associated with distinct myocardial strain patterns, as evidenced by the variation in GLS values. The findings underscore the importance of cardiac monitoring in bipolar disorder, suggesting potential cardiac risks, particularly during the manic phase. This study advocates integrated care approaches, combining psychiatric and cardiac evaluations for patients with bipolar disorder.

Neuropsychological and Neurophysiological Assessment in Different Phases of Bipolar Disorder.

Recent studies have shown that cognitive deficits are significant and pervasive even among remitted bipolar disorder patients. The aim of the current controlled study was to investigate the relationships between cognitive performances, symptom severity, and event-related potentials with regard to different episodes in bipolar patients. This study was conducted on a total of 60 patients diagnosed with bipolar disorder (20 depressive, 20 manic, and 20 in remission). The Frontal Assessment Battery and Stroop test were used for neuropsychological assessment. Event-related potentials were measured using frontal, central, and parietal EEG recordings, while Nihon-Kohden EMG-EP system was used. Delayed P300 latencies were observed in all phases of bipolar disorder when compared to the controls. There was a positive relationship between frontal, central P300 latencies, and Young Mania Rating Scale scores. A strong positive relationship was also observed between Young Mania Rating Scale scores and Stroop interference scores. A negative relationship was observed between Frontal Assessment Battery scores and frontal, central, and parietal N100 latencies and amplitudes in depressed patients. Consistent with these findings, there was a relationship between Hamilton Depression Rating Scale scores and N100 latencies. There was also a positive relationship between Stroop interference scores and central N200 latency, as well as frontal N200 and parietal N200 amplitudes, while a negative relationship was observed between Stroop total time scores and central N200 latency as well as parietal N200 amplitude in depressed patients. Study findings imply that depression episodes could be associated with decision-making autonomy and memory issues, while there is also a relationship between episodes of mania, impaired inhibitory control, and issues with selective attention. Moreover, these cognitive impairments might be included in the initial phases of processing observed in N100 responses in depression, while processing impairment could be pervasive in mania that results in P300 delays.

Роль когнітивно-поведінкової психотерапії в лікуванні Біполярного Розладу

Background. Bipolar disorder (BD) is a chronic, recurrent condition that causes impaired quality of life and disability. This disorder is not only difficult for diagnosis, but also for maintenance and treatment. Apparently the most compliant patients get tired of constant medication. Therefore, it is important to understand how CBT can help patients overcome the shortcomings of pharmacotherapy and better control the various phases of the disease in both acute phase and remission. Results. There are enough techniques in the CBT to monitor symptoms in different phases of BD. Materials. Review of literature on the topic. Conclusions. CBT plays an important role in the maintenance and treatment of bipolar disorder. Living with BD is like running a "marathon" that will never end. If you look at the CBT / psychotherapist and their role in the life of a patient with BD - this is like "relationship" between coach and athlete. It is important to run this "marathon" and try not to go out of the race. This can be done only if you run consciously, calculating your strength, at the right pace to know how to breathe properly, how to find helpful thoughts so as not to fall or overestimate yourself and not make mistakes, how to change running technique, how to keep focus despite fatigue and exhaustion, how to achieve goals. CBT is a "Coach" who teaches how to run properly, technically, how fast, when to take a "break", when to accelerate, when to slow down during a "marathon". In addition, the coach supports, accepts, envy when the athlete is angry or crying from fatigue, wants to give up, but the marathon does not stop. The coach finds the right words, in a good Socratic way, to encourage the athlete not to stop running. And a life-long "marathon" can only be run by a well-trained athlete!

Peripheral levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β across the mood spectrum in bipolar disorder: A meta-analysis of mean differences and variability

ImportanceIt is unclear whether differences exist in the magnitude and variability of pro-inflammatory mediators in the different phases of bipolar disorder (BD) and among subjects with BD, as compared to healthy controls. ObjectiveTo run a comparative meta-analysis of C-Reactive Protein (CRP), IL-1, IL-6, TNF-α in BD vs healthy controls, measuring mean and variability effects on all subjects. Sensitivity analyses include disease activity. Data sourcesSystematic review of observational studies in PubMed and PsycInfo up to February 2nd, 2020. Study selectionCase-control studies reporting inflammatory mediators' levels in BD and controls. Data extraction and synthesisSummary distribution measures of circulating CRP, IL-1β, IL-6, TNF-α in participants with BD and control groups were extracted. Random-effects multivariate meta-analyses were conducted based on individual study/mediator effect sizes (Hedge’s g). Main outcomes and measuresCo-primary outcomes were inflammatory mediators' levels (Hedge’s g) and variability (coefficient of variance ratio (CVR)) differences between participants with BD across the mood spectrum and controls. ResultsOut of the initial 729 papers, 72 were assessed and then excluded after full-text review, and ultimately 53 studies were included in the systematic review, while 49 were included in the meta-analysis. The mean age was 36.96 (SD: 9.29) years, and the mean female percentage was 56.31 (SD: 16.61). CRP (g = 0.70, 95% CI 0.31–1.09, k = 37, BD = 2,215 vs HC = 3,750), IL-6 (g = 0.81, 95% CI 0.46–1.16, k = 45, BD = 1,956 vs HC = 4,106), TNF-α (g = 0.49, 95% CI 0.19–0.78, k = 49, BD = 2,231 vs HC = 3,017) were elevated in subjects with BD vs HC, but not IL-1β (g = -0.28, 95% CI −0.68–0.12, k = 4, BD = 87 vs HC = 66). When considering euthymic, depressive, and manic episodes separately, CRP and TNF-α were elevated in both depressive and manic episodes, but not in euthymia, while IL-6 remained elevated regardless of the disease state. No difference in CVR emerged for CRP, IL-1β, and TNF-α, while a lower CVR was observed for IL-6. When considering disease phases, CVR was higher in BD than in HCs for CRP during depressive episodes, lower for IL-6 during euthymia, and higher during manic episodes for CRP, IL-6, and TNF-α. Sensitivity analyses after excluding outliers identified with funnel plot visual inspection, low-quality studies, and considering only studies matched per body mass index confirmed the main results. Meta-regression showed that age (IL-6, TNF-α), gender (CRP), duration of illness (CRP) moderated elevated individual inflammatory levels. Conclusions and relevancePeripheral pro-inflammatory marker elevations were confirmed in BD. CRP and TNF-α could represent state markers, as they were only elevated during mood episodes, while IL-6 appeared to be a trait marker for BD. Increased variability of specific inflammatory mediators in specific disease active states suggests that a subset of subjects with BD may exhibit elevated inflammation as part of a manic or depressive episode.

New Developments in the Use of Atypical Antipsychotics in the Treatment of Bipolar Disorder: a Systematic Review of Recent Randomized Controlled Trials.

Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD. Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5mg was effective in treating bipolar I depression. Aripiprazole 400mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.

Bipolar Mood State Reflected in Functional Connectivity of the Hate Circuit: A Resting-State Functional Magnetic Resonance Imaging Study.

BackgroundPrevious studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states.MethodsResting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms.ResultsSignificant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms.ConclusionsOur preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.

Connectomic signatures of working memory deficits in depression, mania, and euthymic states of bipolar disorder

BackgroundWorking memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. MethodsWe used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. ResultsAltered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. LimitationsWe used only 2-back load, limiting our ability to study the parametric effects of task demand. ConclusionsWe demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD.

C-reactive protein concentration in bipolar disorder: association with genetic variants

BackgroundSeveral recent studies have investigated the role of C-reactive protein (CRP) in bipolar disorder (BD), but few studies have directly investigated the interaction between CRP genetic variants and peripheral CRP concentration across different phases of BD. In this study, we aimed to replicate previous findings that demonstrated altered CRP levels in BD, and to investigate whether there is an association of peripheral protein expression with genetic variants in the CRP gene.Methods221 patients were included in the study, of which 183 (all episodes, 46 not medicated, 174 medicated) were genotyped for CRP single-nucleotide polymorphisms (SNPs) shown to influence peripheral CRP protein expression (rs1800947, rs2808630, rs1417938, rs1205).ResultsThere were no differences in CRP levels associated with the genotypes, only regarding the rs1205 SNP there were significantly different CRP protein expression between the genotypes when taking body mass index, age, BD polarity, subtype and leukocyte number into account. However, we could show significantly elevated CRP protein expression in manic patients compared to euthymic and depressed patients, independent from genotype. Medication was found to have no effect on CRP protein expression.ConclusionsThese results indicate that low grade inflammation might play a role in mania and might be rather a state than a trait marker of bipolar disorder.

Altered Global Signal Topography and Its Different Regional Localization in Motor Cortex and Hippocampus in Mania and Depression.

Bipolar disorder (BD) is a complex psychiatric disorder characterized by dominant symptom swings across different phases (manic, depressive, and euthymic). Different symptoms in BD such as abnormal episodic memory recall and psychomotor activity have been related to alterations in different regions, ie, hippocampus and motor cortex. How the abnormal regional distribution of neuronal activity relates to specific symptoms remains unclear, however. One possible neuronal mechanism of the relationship is the alteration of the global distribution of neuronal activity manifested in specific local regions; this can be measured as the correlation between the global signal (GS) and local regions. To understand the GS and its relationship to psychopathological symptoms, we here investigated the alteration of both GS variance and its regional topography in healthy controls and 3 phases of BD. We found that the variance of GS showed no significant difference between the 4 groups. In contrast, the GS topography was significantly altered in the different phases of BD, ie, the regions showing abnormally strong topographical GS contribution changed from hippocampus (and parahippocampus/fusiform gyrus) in depression to motor cortex in mania. Importantly, topographical GS changes in these regions correlated with psychopathological measures in both depression and mania. Taken together, our findings demonstrate the central importance of GS topography for psychopathological symptoms. This sheds lights on the neuronal mechanisms of specific psychopathological symptoms in BD, and its relevance in the relationship between global and local neuronal activities for behavior in general.

Randomized Controlled Trials of Psychoeducation Modalities in the Management of Bipolar Disorder: A Systematic Review.

This review sought to summarize the extant literature on the efficacy of 4 modalities of psychoeducation (individual, group, family, internet- based) in the management of patients with bipolar disorder. We searched the digital databases (Science Direct, Scopus, PubMed/MEDLINE) for relevant randomized controlled trials (RCTs) pertaining to psychoeducation in bipolar disorder from inception to February 2017. Keywords and combinations used included psychoeducation, bipolar disorder, individual, family, group, and internet. Reference lists of review articles were also used for retrieval of relevant articles. We retrieved 48 studies and ultimately reviewed 40 RCTs meeting inclusion criteria. Studies were included if they were in English, were RCTs of different psychoeducation modalities managing patients with bipolar disorder, and used standardized assessment of outcomes of psychoeducation. We examined each of the selected publications for relevant data. The majority of psychoeducation RCTs (28 of 40 studies, 70.0%) focused on group and family psychoeducation, with positive benefits reported in clinical outcomes, treatment, and functioning measures. Group psychoeducation was associated with reduced illness recurrences, decreased number and duration of hospitalizations, increased time to illness relapse, better treatment adherence, higher therapeutic lithium levels, and reduced stigma. Family psychoeducation was associated with reductions in illness recurrence, hospitalization rates, and better illness trajectory as well as increased caregiver knowledge, skills, support, and sense of well-being and reduced caregiver burden. There are fewer RCTs on individual and internet-based psychoeducation, with findings being inconsistent or negative. Future studies may include direct comparisons of different psychoeducation modalities to elucidate specific benefits of unique psychoeducation interventions at different phases of bipolar disorder.

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder

BackgroundWhite matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. MethodIn 60 type I BD patients – 20 in manic, 20 in depressive, 20 in euthymic phases – and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. ResultsWe found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. ConclusionsOur data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD.

Actigraphy as an objective intra-individual marker of activity patterns in acute-phase bipolar disorder: a case series

BackgroundActigraphy could be an objective alternative to clinical ratings of motor activity in bipolar disorder (BD), which is of importance now that increased activity and energy are added as cardinal symptoms of (hypo)mania in the DSM-5 and commonly used rating scales give inadequate information about motor symptoms. To date, most actigraphy studies have been conducted in groups and/or used mean activity levels as the variable of interest. The novelty of this case series is therefore to indicate the potential of actigraphy and non-parametric analysis as an objective and personalized marker of intra-individual activity patterns in different phases of BD. To our knowledge, this is the first case series that provides an objective assessment of non-linear dynamics in within-person activity patterns during acute BD episodes.ResultsWe report on three cases of bipolar I disorder with 24-h actigraphy recordings undertaken during the first few days of two or more separate admissions for an acute illness episode, including admissions for individuals in different phases of BD, or with different levels of severity in the same phase of illness. For each recording, we calculated mean activity levels over 24 h, but especially focused on key measures of variability and complexity in activity. Intra-individual activity patterns were found to be different according to phase of illness, but showed consistency within the same phase. With increasing psychotic symptoms, there was evidence of a lower overall level and greater irregularity in activity. As such, sample entropy (a measure of irregularity) may have particular utility in characterizing mania and psychotic symptoms, while assessment of the distribution of rest versus activity over 24 h may distinguish between phases of BD within an individual.ConclusionsThis case series indicates that objective, intra-individual, real-time recordings of patterns of activity may have clinical impact as a valuable adjunct to clinical observation and symptom ratings. We suggest that actigraphy combined with detailed mathematical analysis provides a biological variable that could become an important tool for developing a personalized approach to diagnostics and treatment monitoring in BD.

Pharmacological Treatment Strategies for Acute Bipolar Depression

Of the different phases of bipolar disorder, bipolar depression is more prevailing and is more difficult to treat. However, there is a deficit in...

Bipolar disorder: an overview

Bipolar disorder (BD) is a chronic disorder characterised by abnormal mood changes and fluctuation in energy levels. The disease is characterised by a depressive episode, which can last up to a few months, and include low energy levels, hypersomnia, cognitive impairments, decreased sexual desire, carbohydrate craving, and weight gain. Conversely, bipolar disorder also has a stage of exhilaration and excitement, which can be classified as a manic episode. The typical presentation of these episodes of mania includes high energy hallucinations and delusions, sleep deprivation, fast speech and a constant need to be active. Risk factors that contribute to development of BD include the use of cannabis, influenza during the third trimester of pregnancy, as well as smoking during pregnancy, the use of cocaine, opioids, tranquilisers, stimulants and sedatives during pregnancy, and regular substance use during a period of a year. Parental loss before the age of five, war trauma and stress, as well as traumatic head injury may influence the condition.
 
 Clinical criteria are the mainstay of diagnosis of BD. Differentiating features, which were found to be related to BD, include early age of onset, family history, atypical features and mixed symptoms. Screening tools like the Mood Disorder Questionnaire (MDQ) and Hypomania Checklist (HCL-32) have shown the ability to differentiate BD from major depressive disorder (MDD). 
 
 Treatment differs between the different phases of BD, but lithium can be considered as initial monotherapy, since it is effective against manic, depressive and mixed relapses, and has shown better evidence for prevention of new episodes. It is also associated with a reduced risk of suicide and self-harm in BD patients.

Incidence and predictors of suicide attempts in bipolar I and II disorders: A five-year follow-up

IntroductionAlthough suicidal behavior is very common in bipolar disorder (BD), few long-term studies have investigated incidence and risk factors of suicide attempts (SAs) specifically related to illness phases of BD.ObjectivesWe examined incidence of SAs during different phases of BD in a long-term prospective cohort of bipolar I (BD-I) and II (BD-II) patients and risk factors specifically for SAs during major depressive episodes (MDEs).MethodsIn the Jorvi bipolar study (JoBS), 191 BD-I and BD-II patients were followed using life-chart methodology. Prospective information on SAs of 177 patients (92.7%) during different illness phases was available up to five years. Incidence of SAs and their predictors were investigated using logistic and Poisson regression models. Analyses of risk factors for SAs occurring during MDEs were conducted using two-level random-intercept logistic regression models.ResultsDuring the five-year follow-up, 90 SAs per 718 patient-years occurred. Compared with euthymia the incidence was highest, over 120-fold, during mixed states (765/1000 person-years [95% confidence interval (CI) 461–1269]) and also very high in MDEs, almost 60-fold (354/1000 [95%CI 277–451]). For risk of SAs during MDEs, the duration of MDEs, severity of depression and cluster C personality disorders were significant predictors.ConclusionsIn this long-term study, the highest incidences of SAs occurred in mixed phases and MDEs. The variations in incidence rates between euthymia and illness phases were remarkably large, suggesting that the question “when” rather than “who” may be more relevant for suicide risk in BD. However, risk during MDEs is likely also influenced by personality factors.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Incidence and predictors of suicide attempts in bipolar I and II disorders: A 5‐year follow‐up study

Few long-term studies on bipolar disorder (BD) have investigated the incidence and risk factors of suicide attempts (SAs) specifically related to illness phases. We examined the incidence of SAs during different phases of BD in a long-term prospective cohort of bipolar I (BD-I) and bipolar II (BD-II) patients, and risk factors specifically for SAs during major depressive episodes (MDEs). In the Jorvi Bipolar Study (JoBS), 191 BD-I and BD-II patients were followed using life-chart methodology. Prospective information on SAs of 177 patients (92.7%) during different illness phases was available up to 5years. The incidence of SAs and their predictors were investigated using logistic and Poisson regression models. Analyses of risk factors for SAs occurring during MDEs were conducted using two-level random-intercept logistic regression models. During the 5 years of follow-up, 90 SAs per 718 patient-years occurred. The incidence was highest, over 120-fold higher than in euthymia, during mixed states (765/1000 person-years; 95% confidence interval [CI] 461-1269 person-years), and also very high in MDEs, almost 60-fold higher than in euthymia (354/1000 person-years; 95% CI 277-451 person-years). For risk of SAs during MDEs, the duration of MDEs, severity of depression, and cluster C personality disorders were significant predictors. We confirmed in this long-term study that the highest incidences of SAs occur in mixed and major depressive illness phases. The variations in incidence rates between euthymia and illness phases were remarkably large, suggesting that the question "when" rather than "who" may be more relevant for suicide risk in BD. However, risk during MDEs is likely also influenced by personality factors.

Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania.

Patterns of microstructural white matter abnormalities and their impact on cognitive dysfunction in the various phases of type I bipolar disorder

BackgroundIn recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in type I bipolar disorder (BD). However, WM alterations in the different phases of BD remain to be explored. The aims of this study is to investigate the WM alterations in the various phases of illness and their correlations with clinical and neurocognitive features. MethodsWe investigated the DTI-derived fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) in patients with type I BD (n=61) subdivided in manic (n=21), depressive (n=20) and euthymic phases (n=20) vs. healthy controls (n=42), using a tract-based spatial statistics (TBSS) approach. Then, we investigated whether the subgroups of patients in the various phases of illness present different patterns of WM abnormalities. Finally we studied the correlations between WM alterations and clinical-cognitive parameters. ResultsWe found a widespread alteration in WM microstructure (decrease in FA and increase in MD and RD) in BD when compared to controls. The various subgroups of BD showed different spatial patterns of WM alterations. A gradient of increasing WM abnormalities from the euthymic (low degree and localized WM alterations mainly in the midline structures) to the manic (more diffuse WM alterations affecting both midline and lateral structures) and, finally, to the depressive phase (high degree and widespread WM alterations), was found. Furthermore, the WM diffuse alterations correlated with cognitive deficits in BD, such as decreased fluency prompted by letter and decreased hits and increased omission errors at the continuous performance test. LimitationsPatients under treatment. ConclusionsThe WM alterations in type I BD showed different spatial patterns in the various phases of illness, mainly affecting the active phases, and correlated with some cognitive deficits. This suggests a complex trait- and state-dependent pathogenesis of WM abnormalities in BD.

C.01.03 How to use anxiety, irritability, and agitation (AIA) for diagnosing mania with depressive symptoms – patient cases

Hopelessness, a key risk factor for suicidal behaviour overall, has been studied little among bipolar disorder (BD) patients. For purposes of prevention, it is important to know whether it is predominantly a patient's permanent trait or merely reflects the highly variable illness states. We investigated the degree to which hopelessness is trait- or state-related during the course of BD.The Jorvi Bipolar Study (JoBS) is a naturalistic prospective study representing psychiatric in- and outpatients with DSM-IV BD I and II. Repeated measurements with the Beck Hopelessness Scale of 188 patients at baseline, 6 months and 18 months were analysed using a linear regression model with general estimation equations. Factors covarying with hopelessness during follow-up were investigated.Levels of hopelessness varied markedly between illness phases, being highest in depressive and mixed phases, and lowest in euthymia, hypomania or mania. Hopelessness was independently associated with concurrent severity of depression (estimate 0.231, p < 0.001), anxiety (0.105, p < 0.001), fewer manic symptoms (− 0.096, p = 0.001) and comorbid personality disorder (1.741, p = 0.001). However, the strongest predictor of degree of hopelessness during follow-up was previous hopelessness (0.403, p < 0.001).After baseline, relatively few patients had manic, hypomanic, mixed or depressive mixed phases. Hopelessness was measured at only three time-points.Level of hopelessness varies markedly between patients in different phases of BD, but is also, to a degree, a permanent feature. Among BD patients, hopelessness appears to be both a trait- and state-related characteristic.