Longitudinal Study Of Bipolar Disorder Research Articles

Not missing at random: Missing data are associated with clinical status and trajectories in an electronic monitoring longitudinal study of bipolar disorder

There is limited information on the association between participants' clinical status or trajectories and missing data in electronic monitoring studies of bipolar disorder (BD). We collected self-ratings scales and sensor data in 145 adults with BD. Using a new metric, Missing Data Ratio (MDR), we assessed missing self-rating data and sensor data monitoring activity and sleep. Missing data were lowest for participants in the midst of a depressive episode, intermediate for participants with subsyndromal symptoms, and highest for participants who were euthymic. Over a mean ± SD follow-up of 246 ± 181 days, missing data remained unchanged for participants whose clinical status did not change throughout the study (i.e., those who entered the study in a depressive episode and did not improve, or those who entered the study euthymic and remained euthymic). Conversely, when participants' clinical status changed during the study (e.g., those who entered the study euthymic and experienced the occurrence of a depressive episode), missing data for self-rating scales increased, but not for sensor data. Overall missing data were associated with participants’ clinical status and its changes, suggesting that these are not missing at random.

Longitudinal dynamics between anxiety and depression in bipolar spectrum disorders.

Anxiety and depression are common among individuals with bipolar spectrum disorders (BSDs), with anxiety being a risk factor for depression and vice versa. While the harmful effects of these symptoms are well recognized, their temporal dynamics have not been fully tested. To address this gap, our study investigated bidirectional relationships between anxiety and depression in individuals with BSDs using data from the Prechter Longitudinal Study of Bipolar Disorder, collected over an average of 11 years. We included 651 participants with various BSD subtypes (BD I, BD II, BD not otherwise specified, and schizoaffective bipolar type), with at least 5 years' data for adequate statistical power in detecting temporal dynamics. Bimonthly measurements of anxiety and depression were analyzed using dynamic structural equation modeling. Beyond assessing autoregressive and cross-lagged effects, this study also investigated whether temporal dynamics differed based on demographic characteristics and the use of psychiatric medication. Our findings revealed that individuals with BSDs experienced significant fluctuations in anxiety and depression over time. In addition, we found significant autoregressive and cross-lagged effects of anxiety and depression. Comparison of the cross-lagged effects demonstrated that anxiety had a greater effect on subsequent depression than vice versa. Age and marital status impacted cross-lagged and autoregressive effects. Specifically, older participants had stronger temporal associations between depression and subsequent anxiety, while widowed participants exhibited a heightened impact of depression on subsequent depression. These results underscore the importance of early identification and integrative interventions aimed at addressing both anxiety and depression to mitigate subsequent symptoms in BSDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparative mortality risks in two independent bipolar cohorts

ObjectivesTo compare mortality rates in bipolar disorder with common causes of mortality. MethodsObservational data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD) of 1128 participants including 281 controls was analyzed using logistical regression to quantify mortality rates in comparison with common comorbidities and causes of death. Outcome and treatment measures, including ASRM, GAD-7, PHQ-9 and medication use were used to stratify those with bipolar disorder (BD) that are alive or deceased. A larger cohort of 10,735 existing BD patients with 7,826 controls (no psychiatric diagnosis) from the University of Michigan Health (U-M Health) clinics was used as replication, observational secondary data analysis. ResultsThe mortality rates are significantly different between those with BD and controls in both PLS-BD and U-M Health. Those with BD and are deceased have a higher percentage of elevated depression measures but show no difference in mania or anxiety measures nor medication use patterns. In both cohorts, a diagnosis of BD increases the odds of mortality greater than history of smoking or being older than ≥ 60-years of age. ConclusionBD was found to increase odds of mortality significantly and beyond that of a history of smoking. This finding was replicated in an independent sample.

Interpersonal Trauma and Depression Severity Among Individuals With Bipolar Disorder: Findings From the Prechter Longitudinal Study of Bipolar Disorder.

ABSTRACT Background: Experiences of interpersonal trauma, both in childhood and in adulthood, can affect the trajectory of bipolar disorder (BD). However, the degree to which childhood and/or adult trauma impacts the longitudinal trajectory of depression severity among individuals with BD actively receiving treatment remains unclear. Methods: The effects of childhood trauma (Childhood Trauma Questionnaire) and adult trauma (Life Events Checklist) on depression severity (Hamilton Depression Rating Scale) were investigated in a treatment-receiving subsample with BD (DSM-IV) of the Prechter Longitudinal Study of Bipolar Disorder (2005–present). A mixed-effects linear regression model was used to assess the trajectory of depression severity over 4 years. Results: Depression severity was evaluated in 360 participants, of whom 267 (74.8%) reported a history of interpersonal trauma. A history of childhood trauma alone (n = 110) and childhood and adult trauma combined (n = 108)—but not adult trauma alone (n = 49) —were associated with greater depression severity at the 2-year and 6-year follow-up assessments. However, the trajectory of depression severity (ie, change over time) was similar between participants with a history of childhood trauma, those with a history of adult trauma, and those with no history of interpersonal trauma. Interestingly, participants with a history of both types of trauma showed more improvement in depression severity (ie, from year 2 to year 4: β = 1.67, P = .019). Conclusions: Despite actively receiving treatment for BD, participants with a history of interpersonal trauma—particularly childhood trauma—presented with more severe depressive symptoms at several follow-up assessments. Hence, interpersonal trauma may represent an essential treatment target.

Childhood trauma and depressive symptoms in bipolar disorder: A network analysis.

Childhood trauma is related to an increased number of depressive episodes and more severe depressive symptoms in bipolar disorder. The evaluation of the networks of depressive symptoms-or the patterns of relationships between individual symptoms-among people with bipolar disorder with and without a history of childhood trauma may assist in further clarifying this complex relationship. Data from over 500 participants from the Heinz C. Prechter Longitudinal Study of Bipolar Disorder were used to construct a series of regularised Gaussian Graphical Models. The networks of individual depressive symptoms-self-reported (Patient Health Questionnaire-9; n=543) and clinician-rated (Hamilton Depression Rating Scale-17; n=529)-among participants with bipolar disorder with and without a history of childhood trauma (Childhood Trauma Questionnaire) were characterised and compared. Across the sets of networks, depressed mood consistently emerged as a central symptom (as indicated by strength centrality and expected influence); regardless of participants' history of childhood trauma. Additionally, feelings of worthlessness emerged as a key symptom in the network of self-reported depressive symptoms among participants with-but not without-a history of childhood trauma. The present analyses-although exploratory-provide nuanced insights into the impact of childhood trauma on the presentation of depressive symptoms in bipolar disorder, which have the potential to aid detection and inform targeted intervention development.

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

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

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

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

Covid-19 pandemic and lockdown impacts: A description in a longitudinal study of bipolar disorder

ObjectivesTo investigate the impact of the SAR-Cov-2 pandemic and lockdown on individuals with bipolar disorder in comparison to healthy controls. MethodsA longitudinal study of 560 participants including 147 healthy controls was conducted between April 30 and May 30, 2020 during a state-wide lockdown. Bi-weekly measures included the Coronavirus Impact Scale, the Pittsburg Sleep Quality Index, the Patient Health Questionnaire, 9-item, and the Generalized Anxiety Disorder scale, 7-item. Generalized estimating equations method was used to examine the longitudinal change of the measures within the lockdown and the change from pre-pandemic period to pandemic period. ResultsAll participants reported an impact of lockdown. Individuals with bipolar disorder reported greater impact from the stay-at-home orders with disruptions in routines, income/employment, social support and pandemic related stress. While these measures improved over time, healthy controls recovered quicker and with greater magnitude than persons with bipolar disorder. Comparing mood symptom severity measures in mid-March through May 2020 to the same time window in 2015–2019 (pre- verses post-pandemic), there were no significant differences among individuals with bipolar disorder, whereas healthy controls showed a significant, albeit transient, increase in mood symptoms. ConclusionEveryone was impacted by the SARs-CoV pandemic; however, those with bipolar disorder experienced more life impacting changes from the stay-at-home orders vs healthy controls. These disruptions improved over time but much more slowly than healthy controls.Pre- vs post-pandemic comparisons show a modest but significant increase in mood severity in the healthy controls which was not observed in those with bipolar disorder.

T14 - Digital Phenotyping In Bipolar Disorder

Background Diagnostic categories of psychiatric illnesses based on subjective clinical assessments have been the standard for phenotyping in genetics studies. This is a significant problem for disorders such as bipolar, wherein the course of the illness is an important element of the phenotype. Digit phenotypes, assessed using mobile devices, offer an objective method of gathering data to describe phenotypes for translational research. It has been established that speech patterns are altered in mood disorders. The challenge is to monitor moods over extended periods of time using speech or other mobile-based methods and technology on personal devices. Technology is likely to be incorporated into the ongoing assessment and monitoring of individuals if it is passive and integrated into daily routines; mobile smartphones are ideal. Methods Individuals with rapid cycling bipolar disorder (51) and healthy controls (9) were ascertained from a prospective longitudinal study of bipolar disorder. They were provided with a smartphone pre-loaded with “PRIORI”, an app that securely recorded and encrypted all outgoing speech from all telephone calls sent and received. Two android-based phones were used, the Samsung Galaxy S3 and S5. Weekly assessment calls with a clinician included a depression and mania rating scale (HamD) and (YMRS). The encrypted calls were transferred to a central secure server for processing. Pre-processing included a de-clipping algorithm as it was found that the S3 was “clipping” the audio. The audio was segmented and features of rhythm were extracted and support vector machines were used to classify the speech. This presentation focuses on a subset of 217 acoustic features and solely on assessment calls with the clinician. Results Initial analyses included 37 individuals with two or more episodes wherein HamD > 10 and YMRS 10 and HamD Discussion Digital phenotypes derived from speech captured from mobile devices predict mood states. There are many challenges in addressing the comparability of data collected from across devices with different acoustic sensitivity. We demonstrate that through preprocessing, feature extraction, and data modeling techniques it is possible to mitigate the effects of differing amounts of clipping, loudness, and noise. The goal for a digital phenotyping system is to be passive, requiring no active input from the patient or the clinic. This will greatly improve phenotyping in genetic research over the current methods using structured clinical assessments using standard categorical criteria; digital phenotyping is likely to be able to classify and refine human disease by analyzing physiological patterns (such as speech) over time. However, several confounding factors need to be addressed and the refinement of techniques developed in this study increases device comparability in determining the digital phenotypes.

The effect of poor sleep quality on mood outcome differs between men and women: A longitudinal study of bipolar disorder

BackgroundSleep disturbance is bi-directionally related to mood de-stabilization in bipolar disorder (BD), and sleep quality differs in men and women. We aimed to determine whether perception of poor sleep quality would have a different effect on mood outcome in men versus women. MethodsWe assessed association between sleep quality (Pittsburgh Sleep Quality Index (PSQI)) at study intake and mood outcome over 2 years in subjects from the Prechter Longitudinal Study of Bipolar Disorder (N=216; 29.6% males). The main outcome measure was the severity, variability, and frequency of mood episodes measured by self-report over 2 years of follow-up. Multivariable linear regression models stratified by sex examined the relationship between PSQI with mood outcomes, while age, stressful life events, mood state and neuroticism at baseline were controlled. ResultsIn women, poor sleep quality at baseline predicted increased severity (B=0.28, p<0.001) and frequency of episodes (B=0.32, p<0.001) of depression, and poor sleep quality was a stronger predictor than baseline depression; poor sleep quality predicted increased severity (B=0.19, p<0.05) and variability (B=0.20, p<0.05) of mania, and frequency of mixed episodes (B=0.27, p<0.01). In men, baseline depression and neuroticism were stronger predictors of mood outcome compared to poor sleep quality. LimitationsWe measured perception of sleep quality, but not objective changes in sleep. ConclusionsIn a longitudinal study of BD, women reported poorer perceived sleep quality than men, and poor sleep quality predicted worse mood outcome in BD. Clinicians should be sensitive to addressing sleep complaints in women with BD early in treatment to improve outcome in BD.

Openness predicts cognitive functioning in bipolar disorder

ObjectivesOpenness to experience (O) is a well-established personality factor and is associated with cognitive performance. Little is known about the personality-cognitive relationship in bipolar disorder, an illness with significant variability in mood. Cognitive evaluation is essential in psychopathology assessment as it may reflect underlying disease processes and psychosocial functional capacity. Screening using a proxy personality variable may identify those in need of comprehensive cognitive testing. We hypothesized that O and measures of cognition would associate in both the Bipolar Disorder (BD) and healthy control (HC) samples, whereas neuroticism and extraversion would correlate with cognition only in the BD sample. MethodsData from a longitudinal study of BD were used to study the association between personality factors and cognitive measures of attention, executive functioning, memory and fine motor skills. Regression analyses were used to determine the variables that account for the association between personality and cognition. ResultsAspects of O explained significant cognitive variance (~5%) in both groups; this persisted when demographic variables (including BD versus HC status) were considered. Neuroticism and extraversion did not consistently correlate with cognitive performance in either group. LimitationsThere were more females in the HC group who were slightly younger compared to the BD group. We lack direct measures of positive affect, and there is a reliance on a single measure of personality. ConclusionsBD Individuals scoring low on self-reported Openness are potential candidates for more comprehensive cognitive assessments (which represent a limited resource).

Sleep quality during euthymia in bipolar disorder: the role of clinical features, personality traits, and stressful life events.

BackgroundPoor sleep quality is known to precede the onset of mood episodes and to be associated with poor treatment outcomes in bipolar disorder (BD). We sought to identify modifiable factors that correlate with poor sleep quality in BD independent of residual mood symptoms.MethodsA retrospective analysis was conducted to assess the association between the Pittsburgh Sleep Quality Index and clinical variables of interest in euthymic patients with DSM-IV BD (n = 119) and healthy controls (HC; n = 136) participating in the Prechter Longitudinal Study of Bipolar Disorder. Multivariable linear regression models were constructed to investigate the relationship between sleep quality and demographic and clinical variables in BD and HC participants. A unified model determined independent predictors of sleep quality.Results and discussionEuthymic participants with BD and HC differed in all domains. The best fitting unified multivariable model of poor sleep quality in euthymic participants with BD included rapid cycling (β = .20, p = .03), neuroticism (β = .28, p = 2 × 10−3), and stressful life events (β = .20, p = .02). Poor sleep quality often persists during euthymia and can be a target for treatment. Clinicians should remain vigilant for treating subjective sleep complaints independent of residual mood symptoms in those sensitive to poor sleep quality, including individuals with high neuroticism, rapid cycling, and recent stressful life events. Modifiable factors associated with sleep quality should be targeted directly with psychosocial or somatic treatment. Sleep quality may be a useful outcome measure in BD treatment studies.

Impulsivity, anxiety, and alcohol misuse in bipolar disorder comorbid with eating disorders

BackgroundEating disorders (ED) are noted to occur with bipolar disorder (BD), but relationships between additional comorbidities, clinical correlates, and personality factors common to both remain largely unknown.MethodsUsing data from the Prechter Longitudinal Study of Bipolar Disorder, we measured the prevalence and demographic factors of comorbid ED with BD, presence of additional comorbidity of anxiety and substance use disorders, psychosis, suicide attempts, mixed symptoms, childhood abuse, impact of NEO-Personality Inventory (NEO-PI) personality factors, and mood outcome in 354 patients with BD. We analyzed the prevalence of ED using both broad and narrow criteria.Results and discussionED was more common in the Prechter BD sample than the general population, with the majority of those with ED being female. Anxiety disorders, alcohol abuse/dependence, and NEO-PI N5 impulsiveness were independently associated with ED in a multivariable linear regression analysis. BD age at onset was earlier in the ED group than that in the non-ED group and was earlier than the average onset of ED. Anxiety occurred before ED and alcohol use disorders after both BD and ED. Childhood trauma was associated with ED. Impulsivity and anxiety associated with BD may fuel ED and put patients at risk for other impulsivity-related disorders such as alcohol use disorders. ED was associated with more severe and variable moods and more frequent depression. Patients with BD should be regularly screened for ED, anxiety disorders, and alcohol use disorders, and comorbidity should be promptly addressed.

With More Depressive Episodes Comes More Dementia Risk

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessWith More Depressive Episodes Comes More Dementia RiskJim RosackJim RosackSearch for more papers by this authorPublished Online:17 Dec 2004https://doi.org/10.1176/pn.39.24.00390031aDanish researchers have found that, on average, a patient's risk of developing dementia appears to increase by 13 percent each time the patient is hospitalized for major depression, or by 6 percent for each hospitalization for bipolar disorder.The research, which appeared in the December Journal of Neurology, Neurosurgery, and Psychiatry, appears to complement other work over several decades that indicates some kind of cumulative physiological and/or anatomical insult to the brain with each subsequent episode, Lars Vedel Kessing, M.D., professor of psychiatry at the University of Copenhagen Hospital, said in a press release.“Repeated episodes of depression or bipolar disorder may permanently alter brain tissue—known as the scar hypothesis,” noted Kessing.The results point to the importance of early and sustained treatment to prevent worsening of symptoms, he and his coauthors concluded.The study was funded by the Stanley Medical Research Institute and the Lundbeck Foundation.The authors based their conclusions on records of hospital admissions for severe clinical depression or bipolar disorder between 1970 and 1999 in Denmark, where information on psychiatric illness requiring admission is kept in a national register. They reviewed records of patients identified in the registry as having been admitted and diagnosed with an affective disorder, including a “depressive episode/recurrent depression” and“ manic or mixed episode/bipolar disorder.”At the time of the study ICD-8 or subsequent ICD-10 criteria were used in Denmark. The authors noted “for various reasons” that ICD-9 was never adopted in Denmark. The researchers excluded patients with affective episodes associated with organic brain disease, psychosis, or schizophrenia.In all, nearly 19,000 patients with depression and more than 4,000 patients with bipolar disorder were identified as admitted to the hospital at least once and were included in the study. A diagnosis of dementia at some point after discharge following the initial hospitalization was strongly related to the number of previous admissions for the patient's depression or bipolar disorder.Overall, the incidence of dementia was similar for patients with depression or bipolar disorder. A total of 337 (1.87 percent) of the patients with severe depression went on to be diagnosed with dementia during a subsequent hospitalization, whereas 97 (2.12 percent) of those with bipolar disorder went on to develop dementia.However, the risk of developing dementia was more pronounced for those with depression than for those with bipolar disorder. For every new episode leading to admission, the incidence of dementia increased on average 13 percent for patients with depressive disorder and 6 percent for patients with bipolar disorder.Kessing and his coauthors noted that their findings “are in accordance with the finding of an association between the number of depressive episodes and the risk of developing Alzheimer's disease” in one other longitudinal study, but contrast with the findings of a four-year study that found no significant association.“It is possible that a follow-up of four years is too short,” Kessing noted. “Depression may act as a predictor of dementia, particularly so when there is a large interval between onset of depression and onset of dementia.” Kessing and his coauthors added that “no prior longitudinal study of bipolar disorder has investigated the association between the number of episodes and the risk of developing dementia.”The implications, Kessing wrote, are clear. “If our results can be confirmed in future studies, they underscore the importance of early and sustained prophylaxis of the evolving process of the illness in both depressive and bipolar disorders.”An abstract of the study, “Does the Risk of Developing Dementia Increase With the Number of Episodes in Patients With Depressive Disorder and in Patients With Bipolar Disorder?,” is posted online at<http://jnnp.bmjjournals.com/cgi/content/abstract/75/12/1662?>.▪ J Neurol Neurosurg Psychiatry 2004 75 1662 ISSUES NewArchived