Early Course Of Bipolar Disorder Research Articles

Association between lifetime and recent stressful life events and the early course and psychopathology in patients with newly diagnosed bipolar disorder, first-degree unaffected relatives and healthy controls: Cross-sectional results from a prospective study.

There is an accumulation of stressful life events prior to the first mood episode, but the impact of previous severe life events on psychopathology in patients with bipolar disorder (BD) is not well studied. We aimed to examine the number of recent and lifetime life events in patients with newly diagnosed BD, their unaffected relatives (UR), and healthy controls (HC) as well as the impact of severe lifetime life events on the early course of BD. We compared the number of recent and lifetime life events in 398 patients with newly diagnosed BD, 109 UR, and 214 HC. We subsequently dichotomized the patients with BD by >2 lifetime life events to investigate the associations of severe lifetime life events with clinical characteristics and affective symptoms. Patients with newly diagnosed BD reported significantly more life events in the last 12months and lifetime before compared with UR and HC. Patients who reported >2 lifetime life events (n=160) compared with patients with 0-2 life events (n=238) had a significantly longer diagnostic delay (9.5years±8.2 vs. 6.2years±6.9), presented with more anxiety and depressive symptoms and had at least one previous suicide attempt (30.6% vs. 15.6%) and one previous admission (51.3% vs. 36.6%). The experience of severe lifetime life events seems to impact the early course in BD in terms of longer diagnostic delay, more severe psychopathology including more admissions and a more than doubled risk for previous suicide attempts.

Substance Misuse Trajectories and Risk of Relapse in the Early Course of Bipolar Disorder.

Substance misuse is highly prevalent in bipolar disorder even in the early illness phases. However, the trajectories of misuse of different substances after treatment initiation is not well-studied. Also, knowledge on how substance misuse trajectories influence the early course of bipolar disorder is limited. We recruited 220 individuals in first treatment of bipolar disorder of which 112 participated in a 1-year follow-up study at the NORMENT center in Oslo, Norway. Misuse was defined as having scores above cut-off for harmful use on the Alcohol or Drug Use Disorders Identification Tests (AUDIT or DUDIT). We investigated rates of stopping and continuing misuse of alcohol, cannabis and other illicit substances and daily nicotine use over the follow-up period, and whether such misuse trajectories predicted the risk for affective relapse. The prevalence of cannabis misuse was reduced from 29 to 15% and alcohol misuse was reduced from 39 to 21% during follow-up. Continuing alcohol misuse significantly and independently predicted affective relapse, whereas there was no difference in relapse risk between individuals stopping alcohol misuse and never misusing alcohol. Cannabis misuse trajectories did not significantly predict relapse risk although we cannot exclude interactions with alcohol misuse. In conclusion, substance misuse decreased in the early phase of bipolar disorder treatment but should be further reduced with interventions specifically addressing substance misuse. Stopping alcohol misuse is likely to yield substantial benefit on the clinical course of bipolar disorder.

PREDICTING THE ONSET OF MOOD DISORDERS

The goal of this session is to provide data on parental characteristics and preexisting traits, psychopathology, and other risk factors that are related to the onset or early course of bipolar disorder (BD) in the offspring at high risk.

Course and naturalistic treatment seeking among persons with first episode mania in India: A retrospective chart review with up to five years follow-up

BackgroundAn understanding of the early course of Bipolar Disorder (BD) can contribute towards developing timely interventions. First episode mania (FEM) determines a diagnosis of bipolarity, and therefore, onset of BD-I. We investigated the course of BD-I over a five-year period after FEM by retrospective chart review. MethodsCharts of patients diagnosed with FEM in 2008 (n = 108) were reviewed. Data was extracted about FEM and subsequent course up to 5 years, for those who came for follow-up during this period. The factors influencing course were evaluated with statistical analyses including logistic regression and survival analysis. ResultsThe mean age at onset of BD was 26 ± 9.2 years and mean age at FEM was 27.1 ± 9 years. 41 (38%) patients had previous depression. Patients who returned for at least one follow-up were 60/108 (55.6%), with 54 (90%) of them experiencing another mood episode following FEM. Most recurrences occurred between 6 months to 1 year after FEM, with manic episodes occurring two-three times as frequently as depressive episodes. Good adherence to treatment was a predictor of fewer hospitalizations [B = −0.61; t = −3.1; p = 0.004]. LimitationsThe study was limited by its retrospective design and high number of dropouts. ConclusionThe five-year course after FEM showed twice the number of manic compared to depressive recurrences, irrespective of when the recurrence occurred. Consistent with earlier reports from India, BD-I appears to be mania-predominant, even early in the course. This has significant implications in planning maintenance treatments.

Trajectories of body mass index change in first episode of mania: 3-year data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

BackgroundOverweight/obesity is common in patients with bipolar disorder (BD). However, little is known about longitudinal trends in body mass index (BMI) in patients with BD. Furthermore, most studies on the association between BMI and clinical outcomes are restricted by retrospective and cross-sectional designs. This study uses prospectively-gathered data from a first episode mania (FEM) cohort to examine the trajectories of BMI change and analyze their association with clinical outcomes during a 3-year period. MethodsA total of 110 FEM patients receiving maintenance treatment and 57 healthy subjects were included. The comparisons of BMI trajectories were examined using linear mixed-effects models. The effects of BMI on time to any mood episode were assessed by Cox proportional-hazards models. ResultsThe estimated mean BMI in FEM patients significantly increased from 24.0kg/m2 to 25.4kg/m2 within 6 months. FEM patients had a significant BMI increase trend over the entire 3 years follow-up, which was not observed in the control group. No significant difference in BMI trajectory between patient subgroups (baseline normal-weight vs. overweight/obese; male vs. female) was observed. BMI increase predicted an increased risk of recurrence during follow-up visits (HR=1.50, 95% CI: 1.06–2.13; p=0.02). LimitationsNaturalistic design does not allow the accurate assessments of the impact of pharmacologic treatments on BMI. ConclusionsFEM patients showed a significantly increased BMI trajectory compared to healthy subjects. Furthermore, BMI increase is independently associated with an increased risk of recurrence to a new mood episode during 3-year follow-up. Thus, weight control prevention is needed in the early course of BD.

Continued cannabis use at one year follow up is associated with elevated mood and lower global functioning in bipolar I disorder.

BackgroundThere is limited knowledge about how environmental factors affect the course of bipolar disorder (BD). Cannabis has been proposed as a potential risk factor for poorer course of illness, but the role of cannabis use has not been studied in a first treatment BD I sample.MethodsThe present study examines the associations between course of illness in first treatment BD I and continued cannabis use, from baseline to one year follow up. Patients (N = 62) with first treatment DSM-IV BD I were included as part of the Thematically Organized Psychosis study (TOP), and completed interviews and self-report questionnaires at both baseline and follow up. Cannabis use within the last six months at baseline and use between baseline and follow up (“continued use”) was recorded.ResultsAfter controlling for confounders, continued cannabis use was significantly associated with elevated mood (YMRS) and inferior global functioning (GAF-F) at follow up. Elevated mood mediated the effect of cannabis use on global functioning.ConclusionsThese results suggest that cannabis use has clinical implications for the early course of BD by increasing mood level. More focus on reducing cannabis use in clinical settings seems to be useful for improving outcome in early phase of the disorder.

Treatment in a specialised out-patient mood disorder clinicv.standard out-patient treatment in the early course of bipolar disorder: randomised clinical trial

Little is known about whether treatment in a specialised out-patient mood disorder clinic improves long-term prognosis for patients discharged from initial psychiatric hospital admissions for bipolar disorder. To assess the effect of treatment in a specialised out-patient mood disorder clinic v. standard decentralised psychiatric treatment among patients discharged from one of their first three psychiatric hospital admissions for bipolar disorder. Patients discharged from their first, second or third hospital admission with a single manic episode or bipolar disorder were randomised to treatment in a specialised out-patient mood disorder clinic or standard care (ClinicalTrials.gov: NCT00253071). The primary outcome measure was readmission to hospital, which was obtained from the Danish Psychiatric Central Register. A total of 158 patients with mania/bipolar disorder were included. The rate of readmission to hospital was significantly decreased for patients treated in the mood disorder clinic compared with standard treatment (unadjusted hazard ratio 0.60, 95% CI 0.37-0.97, P = 0.034). Patients treated in the mood disorder clinic more often used a mood stabiliser or an antipsychotic and satisfaction with treatment was more prevalent than among patients who received standard care. Treatment in a specialised mood disorder clinic early in the course of bipolar disorder substantially reduces readmission to a psychiatric hospital and increases satisfaction with care.

Adolescent substance use disorder during the early stages of bipolar disorder: A prospective high-risk study

There is a paucity of longitudinal data characterizing the relationship between substance use disorder (SUD) and the early clinical course of bipolar disorder (BD). We studied this relationship in a prospectively assessed cohort of high-risk offspring. Eligible families had one parent with confirmed BD based on SADS-L interviews and best estimate diagnostic procedure. Offspring completed KSADS-PL interviews at baseline and were reassessed prospectively. DSM-IV diagnoses were made on blind consensus review using all available information. This analysis included 211 offspring ≥12 years, and used GEE and linear mixed models to determine clinical characteristics differentiating those with compared to those without SUD, and CPH models to assess the relationship between SUD and the early stages of BD. Lifetime SUD was diagnosed in 24% of offspring; cannabis use being most common. The peak hazard of SUD was between 14 and 20 years of age. Male sex (HR 3.285; p=.0007), a prior mood disorder (HR 2.437; p=.0091) and parental history of SUD (HR 2.999; p=.0027) contributed to the risk of SUD in the offspring, while SUD predicted an increased risk of psychosis (HR 3.225; p=.0074). The estimated hazard of a major mood disorder in those offspring with compared to those without a prior SUD was almost 3-fold (HR 2.990 (p≤0.01). The novel clinical staging model requires independent replication. SUD is a common comorbidity arising during the early course of BD, even before the first activated episode. Further research is needed to understand causative factors and to develop effective early intervention and prevention strategies.

Resolving the Discrepancy in Childhood Bipolar High-Risk Study Findings

Resolving the Discrepancy in Childhood Bipolar High-Risk Study Findings

Early course of bipolar disorder in high-risk offspring: prospective study

We studied the course of major mood disorders in the offspring of parents with well-characterised bipolar disorder prospectively for up to 15 years. All consenting offspring were assessed annually or anytime symptomatic. The participants began to develop major mood episodes in adolescence and not before. The index major mood episode was almost always depressive, as were the first few recurrences. Onsets and recurrences continued throughout the observation period into adulthood. We did not find evidence of pre-pubertal mania. In summary, adolescence marks the beginning of the high-risk period for major mood episodes related to bipolar disorder.

Neurocognitive functioning in the early stages of bipolar disorder: visual backward masking performance in high risk subjects

Cognitive deficits, including deficits in early information processing, are associated with remitted bipolar disorder. The temporal relationship between these deficits and the clinical course is not known. The current study investigated whether or not deficits in early information processing were present before the onset and/or during the early stages of bipolar disorder. Unaffected and remitted high risk offspring of well-characterized bipolar parents completed a visual backward masking task. For comparison we included a cohort of unaffected offspring of well parents and a clinically referred group of remitted bipolar patients. There was no evidence of a deficit in early information processing in well high risk subjects. As expected, the referred patient group had the highest error rates. After excluding the patients, interaction effect showed that the affected remitted high risk subjects performed differently in terms of error rates than unaffected high risk and control subjects. There were no significant differences in response times across study groups. Exploratory analyses revealed an association between a lifetime history of psychosis and increased errors on the task. There was no evidence of a vulnerability in early information processing in offspring at risk for bipolar disorder. However, there were emergent changes in performance in the affected remitted high risk group. Psychosis appears to be an important clinical correlate associated with cognitive deficits. Mapping of the early course of bipolar disorder and associated changes in cognition has important implications for establishing critical periods for intervention.

Cigarette smoking in the early course of bipolar disorder: association with ages‐at‐onset of alcohol and marijuana use

Despite the high prevalence of smoking among individuals with bipolar disorder, few studies have attempted to identify correlates of smoking status in this group. We examined illness characteristics of bipolar disorder as well as co-occurring alcohol and marijuana use as correlates of cigarette smoking, including the developmental timing of the onset of regular alcohol and cannabis use (i.e., three or more times per week for a month or more). Demographic and clinical characteristics of 134 patients with bipolar I disorder, the majority of whom were adolescents, who were hospitalized for their first manic episode were analyzed to identify correlates of smoking status. A total of 61 (45.5%) of the patients were smokers at the time of their first hospitalization. Smokers were significantly more likely than nonsmokers to report recent use of marijuana (55.7% versus 18.1%) and alcohol (67.2% versus 25.4%). Among those who had ever used marijuana (48.5%) or alcohol (45.5%) regularly, current cigarette smokers reported a significantly earlier age-at-onset of regular use of both substances than reported by nonsmokers. Earlier age-at-onset of marijuana use was the only significant predictor of current smoking in a multivariate analysis. None of the bipolar disorder characteristics examined (i.e., symptom severity, age-at-onset of illness, rapid cycling, and psychosis) were correlated with smoking status. Smoking status in the early course of bipolar disorder is related to both current and past alcohol and marijuana use, but not to characteristics of bipolar illness. Earlier initiation of regular marijuana use is associated with an increased risk of smoking cigarettes.

Outcome following a first manic episode: cross‐national US and Taiwan comparison

Bipolar disorder (BD) is recognized as a significant psychiatric condition worldwide, yet little is known about cross-national differences in the course of illness. This information might clarify features of the disorder that are illness versus culturally specific. Therefore, the aim of this study was to identify differential and shared outcome predictors in first-episode manic bipolar patients in Cincinnati, OH, USA and Taipei, Taiwan. DSM-IV bipolar patients were identified at the time of their first manic or mixed episode and were prospectively followed in a naturalistic, longitudinal study for one year. Patients were recruited from a first psychiatric hospitalization at university-affiliated, urban hospitals in Taipei and Cincinnati. The primary outcome measures were remission, recovery, recurrence and percent of follow-up spent with affective symptoms and syndromes. Treatment adherence was also assessed, as were a number of possible mediator variables. The two patient groups showed a number of significant differences in index clinical presentation on characteristics previously associated with outcome in other studies (e.g., substance abuse). The patients in Taipei showed significantly better outcome on virtually all measures. Some of these findings reflected differences in index (mediator) variables, whereas others persisted after controlling for potential baseline confounds. The early course of BD varies between Chinese and American patients. Some of this variance results from demographic and clinical cross-national differences in premorbid variables. Other sources of variance remain to be identified.

Decreased N-Acetylaspartate in children with familial bipolar disorder

BackgroundRelatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. MethodsSubjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm3 voxels placed in left and right dorsolateral prefrontal cortex. ResultsBipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p < .02). No differences in myoinositol or choline levels were found. ConclusionsChildren and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.