Course Of Illness In Bipolar Disorder Research Articles

Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder.

Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.

The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.

Introduction: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. Methods: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. Results: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). Conclusion: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.

Explaining why childhood abuse is a risk factor for poorer clinical course in bipolar disorder: a path analysis of 923 people with bipolar I disorder.

Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity. We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators. Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data. Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.

Affective Temperament and Seasonality in Bipolar Disorder.

Both affective temperaments and seasonality impact on the illness course in bipolar disorder (BD). This exploratory study aims to investigate the link between seasonality and affective temperament in BD. Sixty-six euthymic patients with BD-I were recruited. The Seasonal Pattern Assessment Questionnaire (SPAQ) and Temperament Evaluation Memphis, Pisa, Paris and San Diego-Autoquestionnaire version scale (TEMPS-A) were applied. The seasonal BD rate was 39.4% (n=26). Depressive and anxious temperament scores were higher in patients with seasonality. The SPAQ total scores were also associated with depressive, cyclothymic, and anxious affective temperament scores. Our findings warrant further investigation to understanding the complex interaction between seasonality, mood regulation, and temperament collectively moderating illness course in BD. This study implies that affective temperament may have some value in discerning the link between seasonality and illness course in BD.

The relation between interhemispheric microstructural deficits and illness course in bipolar disorder

The relation between interhemispheric microstructural deficits and illness course in bipolar disorder

The relationship between self-reported borderline personality features and prospective illness course in bipolar disorder

BackgroundAlthough bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF) and prospective illness course in patients with BD, and explores the effects of current mood state on self-reported BPF profiles.MethodsThe study included 375 patients who participated in the former Stanley Foundation Bipolar Network. All patients met DSM-IV criteria for bipolar-I disorder (n = 294), bipolar-II disorder (n = 72) or bipolar disorder NOS (n = 9). BPF were assessed with the self-rated Personality Diagnostic Questionnaire. Illness course was based on 1-year clinician rated prospective daily mood ratings with the life chart methodology. Regression analyses were used to estimate the relationships among these variables.ResultsAlthough correlations were weak, results showed that having more BPF at baseline is associated with a higher episode frequency during subsequent 1-year follow-up. Of the nine BPF, affective instability, impulsivity, and self-mutilation/suicidality showed a relationship to full-duration as well as brief episode frequency. In contrast all other BPF were not related to episode frequency.ConclusionsHaving more BPF was associated with an unfavorable illness course of BD. Affective instability, impulsivity, and self-mutilation/suicidality are associated with both rapid cycling BD and BPD. Still, many core features of BPD show no relationship to rapid cycling BD and can help in the differential diagnosis.

Menopause and illness course in bipolar disorder: A systematic review.

Menopause may be a time of increased mood symptoms for some women. This systematic review aimed to examine the severity of symptoms and prevalence of mood changes in women with bipolar disorder during peri-menopause and post-menopause. A systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The two primary outcomes assessed were relapse rates and symptom severity during menopause. Databases searched were MEDLINE, EMBASE, PsychInfo, CINAHL and SCOPUS from January 1980 until December 2016. Nine studies, including a total of 273 participants diagnosed with bipolar disorder and who reported menopause, were included in the narrative synthesis. Menopause was reported to be associated with increased symptoms overall, and with depression in particular (range of 46%-91%). The collection of self-reported retrospective data was the most commonly used method to record menopause status. The impact of menopause on illness course for women with bipolar disorder is largely under-explored. Preliminary evidence suggests that it may be associated with increased bipolar symptoms. Further work is needed to explore how menopause may interact with bipolar disorder over time and the nature of these symptom changes, and if and how menopause may differ from other reproductive stages.

Psychoeducation and online mood tracking for patients with bipolar disorder: A randomised controlled trial

BackgroundPsychoeducation is an effective adjunct to medications in bipolar disorder (BD). Brief psychoeducational approaches have been shown to improve early identification of relapse. However, the optimal method of delivery of psychoeducation remains uncertain. Here, our objective was to compare a short therapist-facilitated vs. self-directed psychoeducational intervention for BD. MethodsBD outpatients who were receiving medication-based treatment were randomly assigned to 5 psychoeducation sessions administered by a therapist (Facilitated Integrated Mood Management; FIMM; n=60), or self-administered psychoeducation (Manualized Integrated Mood Management; MIMM; n=61). Follow-up was based on patients’ weekly responses to an electronic mood monitoring programme over 12 months. ResultsOver follow-up, there were no group differences in weekly self-rated depression symptoms or relapse/readmission rates. However, knowledge of BD (assessed with the Oxford Bipolar Knowledge questionnaire (OBQ)) was greater in the FIMM than the MIMM group at 3 months. Greater illness knowledge at 3 months was related to a higher proportion of weeks well over 12 months. LimitationsFeatures of the trial may have reduced the sensitivity to our psychoeducation approach, including that BD participants had been previously engaged in self-monitoring. ConclusionsImproved OBQ score, while accelerated by a short course of therapist-administered psychoeducation (FIMM), was seen after both treatments. It was associated with better outcome assessed as weeks well. When developing and testing a new psychosocial intervention, studies should consider proximal outcomes (e.g., acquired knowledge) and their short-term impact on illness course in bipolar disorder.

Adipokines, metabolic dysfunction and illness course in bipolar disorder

Replicated evidence indicates that individuals with BD are differentially affected by metabolic comorbidities and that its occurrence is a critical mediator and/or moderator of BD outcomes. This study aimed to explore the role of adipokines on bipolar disorder (BD) course and its relationship with metabolic comorbidities (i.e. type 2 diabetes mellitus, obesity). We measured plasma levels of adiponectin and leptin, as well as anthropometric and metabolic parameters of 59 patients with BD and 28 healthy volunteers. Our results showed that, in female participants, adiponectin was lower in individuals with BD, relative to healthy controls (p = 0.017). In the BD population, adiponectin levels were correlated with fasting glucose (r = −0.291, p = 0.047), fasting insulin (r = −0.332, p = 0.023), C-peptide (r = 0.040, p = 0.040), homeostatic model assessment-insulin resistance (r = −0.411, p = 0.004), HDL (r = 0.508, p < 0.001), VLDL (r = −0.395, p = 0.005) and triglycerides (r = −0.310, p = 0.030). After adjustment for age, gender and BMI, individuals with BD and low adiponectin levels (i.e. < 7.5 μg/ml), had a higher number of mood episodes (p < 0.001), lower number of psychiatric hospitalizations (p = 0.007), higher depressive symptoms (p < 0.001) and lower levels of functioning (p = 0.020). In conclusion, adiponectin levels, either directly or as a proxy of metabolic dysfunction, is independently associated with an unfavorable course of illness in BD.

Valuing happiness is associated with bipolar disorder.

Although people who experience happiness tend to have better psychological health, people who value happiness to an extreme tend to have worse psychological health, including more depression. We propose that the extreme valuing of happiness may be a general risk factor for mood disturbances, both depressive and manic. To test this hypothesis, we examined the relationship between the extreme valuing of happiness and risk for, diagnosis of, and illness course for bipolar disorder (BD). Supporting our hypothesis, the extreme valuing of happiness was associated with a measure of increased risk for developing BD (Studies 1 and 2), increased likelihood of past diagnosis of BD (Studies 2 and 3), and worse prospective illness course in BD (Study 3), even when controlling for current mood symptoms (Studies 1-3). These findings indicate that the extreme valuing of happiness is associated with and even predicts BD. Taken together with previous evidence, these findings suggest that the extreme valuing of happiness is a general risk factor for mood disturbances. More broadly, what emotions people strive to feel may play a critical role in psychological health.

Food Craving in Bipolar Disorder

Objectives Food craving (FC) has been linked todepressive mood before. However, no study exists evaluating FC in a sample of bipolar disorder (BD). Aims This study aimed to determine the prevalence of FC in individuals with BD during euthymia. Methods Fifty individuals with a BD diagnosis according to the DSM-IV guidelines were drawn from the dedicated outpatient center of the University Clinic of Psychiatry Graz. Data were compared with data from a healthy control sample (HC, n=50). All probands took part in the BIPFAT study exploring shared pathophysiological pathways of obesity and brain function in BD. Participants completed a comprehensive diagnostic battery (including the Food Craving Questionnaire by White et al. 2002) measuring anamnestic, anthropometric, and clinical data. We performed a MANCOVA controlling for key covariates including gender, age, body mass index, smoking, mood stabilizing medication, and lipid levels. Results BD patients exhibited significantly more total food craving ( F =6.10, p =.016) and more sweets craving than controls ( F =6.38, p =.014). Additionally, levels of fat craving were higher by trend in the male patient group than in the male control group ( F =3.15, p =.087). Conclusions A higher prevalence of FC in BD patients than in controls suggests that FC may be of clinical importance in BD. Potentially, FC plays a role in the development of obesity, a well-known risk factor for unfavorable course of illness in BD. Furthermore, the impact of dysfunctions in the serotonergic system and/or an altered activation of the hypothalamic-pituitary-adrenal axis in relationship to increased FC are critically discussed.

White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5-HTTLPR.

Bipolar disorder (BD) is associated with signs of widespread disruption of white matter (WM) integrity. A polymorphism in the promoter of the serotonin transporter (5-HTTLPR) influenced functional cortico-limbic connectivity in healthy subjects and course of illness in BD, with the short (s) allele being associated with lower functional connectivity, and with earlier onset of illness and poor response to treatment. We tested the effects of 5-HTTLPR on diffusion tensor imaging (DTI) measures of WM microstructure in 140 inpatients, affected by a major depressive episode in course of BD, of Italian descent. We used whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity and fractional anisotropy. Compared with l/l homozygotes, 5-HTTLPR*s carriers showed significantly increased radial and mean diffusivity in several brain WM tracts, including corpus callosum, cingulum bundle, uncinate fasciculus, corona radiata, thalamic radiation, inferior and superior longitudinal fasciculus and inferior fronto-occipital fasciculus. An increase of mean and radial diffusivity, perpendicular to the main axis of the WM tract, is thought to signify increased space between fibers, thus suggesting demyelination or dysmyelination, or loss of bundle coherence. The effects of 5-HTTLPR on the anomalous emotional processing in BD might be mediated by changes of WM microstructure in key WM tracts contributing to the functional integrity of the brain.

Cannabis use may worsen illness course in bipolar disorder

Cannabis use may worsen illness course in bipolar disorder

Psychosocial predictors of mood symptoms 1 year after acute phase treatment of bipolar I disorder

Objective The aim of the current study was to evaluate family functioning, social support, and functional impairment as predictors of mood symptoms 1 year after acute phase treatment of bipolar I disorder. This study builds upon the extant literature by evaluating these putative psychosocial risk factors simultaneously to determine whether they account for unique variance in clinical outcomes. Method Patients (N = 92) were recruited from hospital settings during an acute mood episode to participate in pharmacologic or combined family and pharmacologic interventions. The Modified Hamilton Rating Scale for Depression, Bech-Rafaelson Mania Scale, Family Assessment Device, Interpersonal Support Evaluation List, and UCLA Social Attainment Survey were administered at acute phase treatment completion and again at 1-year follow-up. Controlling for mood symptom severity at acute phase treatment completion, multiple regression analyses were used to examine longitudinal associations between the psychosocial variables and subsequent depressive and manic symptoms. Results None of the aforementioned psychosocial variables predicted manic symptomatology, and social support alone emerged as a unique predictor of depression at the 1-year follow-up. Effects of social support were moderated by recovery status, such that the strength of association between social support and subsequent depression was stronger for those who had not fully recovered during the acute phase of treatment than for those who had. Conclusions Low levels of social support at acute phase treatment completion, especially in concert with residual symptomatology, may place individuals with bipolar I disorder at risk for subsequent depressive symptoms. These data suggest that maintenance therapies focused on improving level of social support might be especially important to consider in the management of bipolar depression, and add to a growing literature focused on unique vs shared effects of psychosocial risk factors for poor illness course in bipolar disorder.

State- and trait-related deficits in sustained attention in bipolar disorder.

Investigation of neuropsychological functioning in bipolar disorder provides a potential link from the prominent cognitive symptoms of the disorder to the underlying neural mechanisms. Continuous performance measures of sustained attention have yielded consistent findings in bipolar disorder patients. There are impairments that appear to be both state- and trait-related. Impaired target detection may represent one of the most sensitive markers of illness course in bipolardisorder. It is unrelated to residual mood symptomatology and medication status, and is present in patients with good functional recovery. The impairment in target detection is exacerbated in the manic state, and is accompanied by an increased rate of false responding. Sustained attention deficit is present early in the course of the disorder, but becomes more pronounced with repeated episodes. This cognitive profile, of an early-onset, state-modulated, trait marker, is distinct from the profile of attentional disruption seen in schizophrenia or unipolar depression. The state- and trait-related impairments may be differentially associated with the ascending dopamine and noradrenaline projections.