Recurrent Bipolar Disorder Research Articles

Resilience and impulsivity in euthymic patients with bipolar disorder

BackgroundStress plays an important role in the onset and recurrence of bipolar disorder (BD). Resilience is the ability to cope with stress or adversity. Few studies have examined resilience in BD, and this study aimed to investigate the clinical correlates of resilience in euthymic patients with BD. MethodsA total of 62 outpatients with BD type I, II, and not otherwise specified (NOS) who were in remission and 62 healthy individuals matched with the BD group in terms of age and sex were recruited. All participants completed the Connor–Davidson Resilience Scale and Barratt Impulsiveness Scale. A psychiatrist interviewed the subjects to assess clinical characteristics. Multiple linear regression analysis was used to determine factors associated with resilience. ResultsThe BD group had significantly higher levels of impulsivity and lower levels of resilience compared with the control group. Degree of impulsivity, number of depressive episodes, Clinical Global Impression (CGI) scores, and length of education were significantly correlated with resilience. Attention impulsivity, non-planning impulsivity, and number of depressive episodes were associated with low levels of resilience, even when age, sex, length of education, and CGI scores were controlled. LimitationsBecause tertiary hospital patients were recruited, the generalizability of the findings is limited. ConclusionsThis study shows that low levels of resilience are related to high levels of impulsivity and to an increased number of depressive episodes in euthymic patients with BD. Given the reciprocal relationship between resilience and impulsivity, efforts to enhance resilience and reduce impulsivity may make important contributions to the treatment of patients with BD.

Olanzapine discontinuation emergent recurrence in bipolar disorder.

Objective:The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear.Materials and Methods:Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review.Results:There was no correlation found between the period of tapering olanzapine, time to recurrence of episode after discontinuation, and the dosage of olanzapine at the time of discontinuation. The predominant early signs of relapse after discontinuation of olanzapine included sleep disturbance (72.7%), lack of insight for change in behavior (72.7%), irritability (54.5%), and elevated mood (45.5%).Conclusion:Mood stabilizer alone as a maintenance therapy of bipolar disorder may be inadequate for long-term management. A low dose of olanzapine along with mood stabilizers might be useful for prevention of recurrence in bipolar disorder.

Response to Lithium in Bipolar Disorder: Clinical and Genetic Findings

The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one-third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristics were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric comorbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so-called "candidate" gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. We demonstrated that response to lithium has been connected with the genotype of BDNF gene and serum BDNF levels and have shown that ELR have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on lithium response. The Consortium on Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of lithium response in BD, and the first results have already been published.

The evolution of psychoeducation for bipolar disorder: from lithium clinics to integrative psychoeducation

Coping and living with bipolar disorder is complex and sometimes counterintuitive. It demands a number of attitudes and aptitudes that include a huge emotional insight, healthy and regular lifestyle, skills to identify subtle changes and motivation to reach full treatment adherence. Patients' engagement and proactive attitude are a must for a successful therapeutic outcome. This may partly explain the therapeutic impact of psychoeducational programs in this disorder. However, the history of group psychoeducation in bipolar disorder is full of ups and downs. Interestingly enough, worldwide-respected opinion leaders in group therapy were initially not very enthusiastic with the use of such strategy with bipolar patients. I. Yalom, for instance, defined a bipolar patient as “one of the worst calamities that could befall group therapy” 1. Since then, the practice of psychoeducation has been evolving together with the conceptualization of bipolar disorder.

Abnormal functional connectivity of the medial cortex in euthymic bipolar II disorder

This project utilized functional MRI (fMRI) and a motor activation paradigm to investigate neural circuitry in euthymic bipolar II disorder. We hypothesized that circuitry involving the cortical midline structures (CMS) would demonstrate abnormal functional connectivity. Nineteen subjects with recurrent bipolar disorder and 18 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We found increased functional connectivity among bipolar subjects compared to healthy controls in two CMS circuits. One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus and the right medial frontal gyrus and surrounding region. Our results indicate that CMS circuit dysfunction persists in the euthymic state and thus may represent trait pathology. Future studies should address whether these circuits contribute to relapse of illness. Our results also suggest the possibility that aberrations of superior frontal circuitry may impact default mode network and cognitive processes.

Genetic Influences on Response to Mood Stabilizers in Bipolar Disorder

Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990s, form the second generation of such drugs. The response of patients with bipolar disorder to mood stabilizers has different levels of magnitude. About one-third of lithium-treated patients are excellent responders, showing total prevention of the episodes, and these patients are clinically characterized by an episodic clinical course, complete remission, a bipolar family history, low psychiatric co-morbidity and a hyperthymic temperament. It has been suggested that responders to carbamazepine or lamotrigine may differ clinically from responders to lithium. The main phenotype of the response to mood stabilizers is a degree of prevention against recurrences of manic and depressive episodes during long-term treatment. The most specific scale in this respect is the so-called Alda scale, where retrospective assessment of lithium response is scored on a 0–10 scale. The vast majority of data on genetic influences on the response to mood stabilizers has been gathered in relation to lithium. The studies on the mechanisms of action of lithium and on the neurobiology of bipolar disorder have led to the identification of a number of candidate genes. The genes studied for their association with lithium response have been those connected with neurotransmitters (serotonin, dopamine and glutamate), second messengers (phosphatidyl inositol [PI], cyclic adenosine-monophosphate [cAMP] and protein kinase C [PKC] pathways), substances involved in neuroprotection (brain-derived neurotrophic factor [BDNF] and glycogen synthase kinase 3-β [GSK-3β]) and a number of other miscellaneous genes. There are no published pharmacogenomic studies of mood stabilizers other than lithium, except for one study of the X-box binding protein 1 (XBP1) gene in relation to the efficacy of valproate. In recent years, a number of genome-wide association studies (GWAS) in bipolar disorders have been performed and some of those have also focused on lithium response. They suggest roles for the glutamatergic receptor AMPA (GRIA2) gene and the amiloride-sensitive cation channel 1 neuronal (ACCN1) gene in long-term lithium response. A promise for better elucidating the genetics of lithium response has been created by the formation of the Consortium on Lithium Genetics (ConLiGen) to establish the largest sample, to date, for the GWAS of lithium response in bipolar disorder. The sample currently comprises more than 1,200 patients, characterized by their response to lithium treatment according to the Alda scale. Preliminary results from this international study suggest a possible involvement of the sodium bicarbonate transporter (SLC4A10) gene in lithium response. It is concluded that the pharmacogenetics of response to mood stabilizers has recently become a growing field of research, especially so far as the pharmacogenetics of the response to lithium is concerned. Clearly, the ConLiGen project is a highly significant step in this research. Although the results of pharmacogenetic studies are of significant scientific value, their possible practical implications are yet to be seen.

A Simple Question Answered: Adding Moderate-Dosage Lithium Does Not Help Patients With Bipolar Disorder

A Simple Question Answered: Adding Moderate-Dosage Lithium Does Not Help Patients With Bipolar Disorder

Relationship between neurocognitive functioning and episode recurrences in bipolar disorder

BackgroundThe relationship between neurocognitive impairment and clinical course in bipolar disorder (BD) is inconclusive. The aim of this study was to compare time to recurrence between patients with and without clinically significant cognitive impairment. MethodsSeventy euthymic patients with BD were included. Based on baseline neurocognitive performance, patients were divided into those with (n=49) and those without (n=21) clinically significant cognitive impairment. Both groups of patients were prospectivelly assessed by a modified life chart method during a mean of 16.3 months. ResultsPatients with some cognitive domain compromised had an increased risk of suffering any recurrence (HR: 3.13; CI 95%: 1.64–5.96), hypo/manic episodes (HR: 2.42; CI 95%: 1.13–5.19), or depressive episodes (HR: 3.84, CI 95%: 1.66–8.84) compared with those patients without clinically significant cognitive impairment. These associations remained significant after adjusting for several potential counfounders such as number of previous episodes, time since last episode, clinical subtype of BD, exposure to antipsychotics, and subclinical symptoms. LimitationsWe classified patients as with or without clinically significant cognitive impairment, although deficits in different cognitive domains may not be equivalent in terms of risk of recurrence. ConclusionsThe results did not support the hypothesis that the experience of successive episodes is related to a progressive neurocognitive decline. On the contrary, cognitive impairment could be the cause more than the consequence of poorer clinical course. Alternatively, a specific subgroup of patients with clinically significant cognitive impairment and a progressive illness in terms of counts of recurrence and shortening of wellness intervals might explain the association showed in this study.

Predictors of recurrence in bipolar disorders in Spain (PREBIS study data)

The objective of this study was to evaluate demographic, psychosocial and clinical predictors of mood recurrences in bipolar disorder (BD) euthymic outpatients followed-up for 12 months in a naturalistic setting. The study included 595 consecutive BD patients, diagnosed according to DSM-IV-TR criteria, in clinical remission at baseline. Quarterly assessments were scheduled. Clinical evaluation as well as mood and functioning psychometric evaluations were performed. We applied logistic regression analysis to determine predictors of presenting an affective recurrence, and Cox regression analysis to examine the association between individual predictors and time to affective recurrence. Of the 593 patients finally included (60% women, 84.5% BD I), 141 (23.78%) had at least a recurrence during the 12 months follow-up. Time until 25% of the patients experienced a recurrence was 12 months (95% CI: 9.14-undetermined). In multivariate analysis, factors significantly related to relapse were living setting (p=0.002) and total number of previous episodes (p=0.01). Residents in mixed urban/rural catchment areas had 57% more risk than dwellers of cities with more than 100,000 people, and a higher number of previous episodes also increased the relapse risk. A shorter time to relapse was related to job status (p=0.004) and to living setting (p=0.002). In our sample, living in environments of less than 100,000 inhabitants and having more previous affective episodes were related to an increased relapse risk in BD, and job status and living setting were related to a shorter time to relapse. No specific contemporary practice guidelines were used. Drug treatment and plasma levels, although measured, were not registered.

Screening for the markers of kidney damage in men and women on long-term lithium treatment.

SummaryBackgroundLithium is the most effective therapeutic modality for the prevention of recurrences in bipolar disorder. An important adverse effect of lithium, especially with long-term treatment, is a possibility of a toxic effect on kidney function. Therefore, the aim of the study was to assess kidney function in a group of long-term lithium-treated patients.Material/MethodsThe study comprised 80 patients with bipolar mood disorder (26 male, 54 female), aged 60±11 years. They had been receiving lithium for 5–38 (16±9) years. Random urine sample was examined for albumin and creatinine excretion, and urinary albumin to creatinine ratio (UACR) was calculated. Specific gravity of the urine sample was recorded. Serum concentration of creatinine was measured and estimated glomerular filtration rate (eGFR) was calculated. Serum concentration of albumin was also measured.ResultsDecreased eGFR values <60 ml/min/1.73 m2 were found in 23% of patients, significantly more frequently in men that in women (38% vs. 16%, p=0.04). Elevated UACR values (>30 mg/g) were found in 25% of men and 12% of women, respectively. Serum albumin concentration >52 g/l was detected in 19% of patients (17% of men and 20% of women). Specific gravity of the urine, equal to or below 1.005, was recorded in 21% of men and 14% of women.ConclusionsThe results confirm the opinion that screening for the markers of kidney damage should be performed in long-term lithium-treated patients for identification of persons with impaired kidney function. Male sex seems to be the risk factor for the development of kidney damage during long-term lithium treatment.

P-193 - Employment outcomes in people with bipolar disorder: a systematic review

Objectives We conducted a systematic review in order to identify the long term employment outcomes of people with Bipolar Disorder. Our aims were to identify the proportions working over time, the nature of employment status change over time and whether employment rates after a single episode are different to rates in recurrent Bipolar Disorder. Methods We searched Medline, PsychInfo and Web of Science databases and used a predetermined decision tree to select papers for full text usage. Results Out of 1410 abstracts retrieved, a total of 119 papers were selected for full text retrieval and 19 papers identified which met the full criteria for inclusion and data extraction. An assessment framework to assess the quality of papers was used to aid the analysis. There were few high quality studies. Most studies with samples of people with established Bipolar Disorder suggest that over a period of 5–15 years of follow-up, approximately 40–60% of people were in employment. However Bipolar Disorder appears to lead to underperformance whilst in employment and 40–50% of people may suffer a slide of their occupational status over time. Those with a first episode of Bipolar Disorder had a higher rate of employment than those with multiple episodes. Conclusions Bipolar disorders damage employment prospects for sufferers in the short and longer term, but up to around 60% of people may be able to recover to the extent that they are in paid work. Maximal damage to employment functioning may occur in the early phases of Bipolar Disorder.

Benzodiazepine Use and Risk of Recurrence in Bipolar Disorder: A STEP-BD Report

Benzodiazepine Use and Risk of Recurrence in Bipolar Disorder: A STEP-BD Report

Predictors of recurrence of bipolar disorder during pregnancy and postpartum periods in a sample of Egyptian women

Predictors of recurrence of bipolar disorder during pregnancy and postpartum periods in a sample of Egyptian women

Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample

Background We analyzed the association of previous course-of-illness and other variables of clinical interest with a high frequency of both depressive or (hypo)manic episodes controlling for the effect of socio-demographic characteristics. Methods A total of 108 outpatients with a DSM-IV diagnosis of bipolar disorder (BD) were recruited. A retrospective and naturalistic study was conducted to examine the number of affective episodes and their relationship with socio-demographic, clinical and course-of-illness variables, including adherence to medication, type of medication used and the use of addictive substances. The episode frequency was estimated as the number of “major instances” of depression, hypomania and mania during the illness. To classify the patients into two groups (higher and lower-episode frequency), we used the statistical criterion of median split. Results were analyzed with logistic regression models to control for the effects of potential confounders. Results A high episode frequency (nine or more episodes) was associated with age (36–55 years), delay in diagnosis, poor adherence to medication and current use of antipsychotic medication. In addition, a high frequency of manic episodes (four or more) was associated with female sex, age (> 36 years) and a manic onset of the illness, whereas a high frequency of depressive episodes (five or more) was associated with delay in diagnosis and poor adherence to medication. Limitations Cross-sectional study design. Conclusions Avoiding delay in diagnosis and enhancing treatment adherence might be important targets for reducing recurrences in BD.

Impaired theory of mind performance in patients with recurrent bipolar disorder: Moderating effect of cognitive load

The aim of this study was to investigate theory of mind (ToM) performance on tasks that varied in the demands they placed on cognitive processing resources in a sample of 14 bipolar patients with subsyndromal illness and 14 controls. Patients showed impaired performance on cognitively demanding second-order ToM tasks. Reduced ToM performance was associated with longer illness duration, and with increased symptom severity.

Benzodiazepine use and risk of recurrence in bipolar disorder: a STEP-BD report.

Benzodiazepines are widely prescribed to patients with bipolar disorder, but their impact on relapse and recurrence has not been examined. We examined prospective data from a cohort of DSM-IV bipolar I and II patients who achieved remission during evidence-guided naturalistic treatment in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study (conducted in the United States between 1999 and 2005). Risk for recurrence among individuals who did or did not receive benzodiazepine treatment was examined using survival analysis. Cox regression was used to adjust for clinical and sociodemographic covariates. Propensity score analysis was used in a confirmatory analysis to address the possible impact of confounding variables. Of 1,365 subjects, 349 (25.6%) were prescribed a benzodiazepine at time of remission from a mood episode. After adjusting for potential confounding variables, the hazard ratio for mood episode recurrence among benzodiazepine-treated patients was 1.21 (95% CI, 1.01-1.45). The effects of benzodiazepine treatment on relapse remained significant after excluding relapses occurring within 90 days of recovery, or stratifying the sample by propensity score, a summary measure of likelihood of receiving benzodiazepine treatment. In an independent cohort of 721 subjects already in remission at study entry, effects of similar magnitude were observed. Benzodiazepine use may be associated with greater risk for recurrence of a mood episode among patients with bipolar I and II disorder. The prescribing of benzodiazepines, at a minimum, appears to be a marker for a more severe course of illness.

Long-term efficacy of a psychological intervention program for patients with refractory bipolar disorder: A pilot study

The aim of this research was to test the long-term efficacy of combined standard treatment (pharmacotherapy and adjunctive psychosocial treatment based on a cognitive-behavioral model) compared with standard drug treatment for patients with recurrent bipolar disorder. Twenty patients selected according to DSM-IV-TR criteria were randomized to 1) combined treatment or 2) control treatment. A multigroup experimental design with repeated assessment measures (pre-treatment, post-treatment, 6-month follow-up, and 12-month follow-up) was used. Results of the repeated measurement analysis showed a significant increment in scores of Global Activity Functioning within the combined treatment group during the follow-up, which was not observed in the control treatment group. Therefore, the effectiveness of psychotherapy tends to increase with time, and this improvement is not significant until 12 months of follow-up.

Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A retrospective naturalistic study

In bipolar disorder the discontinuation of lithium prophylaxis is associated with early episode precipitation. Is this ;rebound' phenomenon peculiar to lithium? This naturalistic retrospective case note review investigated the frequency of immediate recurrence after discontinuation of any prophylactic treatment. Bipolar patients who stopped at least one medication after at least 6 months of remission were studied. A total of 310 case notes were examined in a systematic search. A total of 53 cases of discontinuation in 48 subjects were found. Discontinued medications included lithium, valproate, carbamazepine, typical and atypical antipsychotics and antidepressants. Recurrence occurred within 3 months of medication withdrawal in 39 cases (74%). Over half of the discontinuation episodes involved lithium: recurrence occurred in 86% of these cases. In the groups stopping other prophylactic agents, a majority of subjects suffered recurrence: anticonvulsants (89%), antipsychotics (64%) and antidepressants (58%). However, these groups were small and the clarity of the data was undermined by the simultaneous withdrawal of other agents. Manic and hypomanic episodes were the most common form of recurrences. Depressive episodes occurred proportionately most frequently following antidepressant withdrawal. More than half of recurrences required hospital admission. This study provides preliminary naturalistic evidence that early episode recurrence in bipolar disorder is not peculiar to lithium withdrawal but may occur following withdrawal of medication from all classes recommended in prophylaxis. These findings, if replicated, have important implications for clinical practice and for research.

Récurrences dans les troubles bipolaires – Étude comparative à partir d’une population âgée de 65 ans et plus entre troubles bipolaires, troubles dépressifs récurrents et épisodes dépressifs simples

Bipolar mood disorders, after starting at adulthood, may remain active throughout life, but bipolar disorders may only be revealed in later life. Indeed, Yet few data on bipolar disorders in the elderly have been reported in the litterature. The influence of normal aging on the outcome of the disease as well as the specific prognosis of bipolar disorders in the elderly has occasionally been studied. Eventually Finally, and contrasting with adults, few studies comparing the various subtypes of mood disorders were have been performed in the elderly. We therefore developed a study in patients aged 65 or above, in order to evaluate the course (recurrences) of bipolar disorders, compared to recurring depressions and single depressions, and to determine the influence of recurrences on the outcome of bipolar disorders. Patients aged over 65 years were inpatients admitted to the department of psychiatry in 2000 for one of the three previously mentioned diagnoses according to DSM IV. Retrospective data were collected from medical reports. Prospectively, data were collected from the general practitioner of each patient (relying on telephone calls), before statistical analysis was performed. Our study demonstrates a more severe outcome for bipolar disorders compared to recurring depressions and single depressions. Patients with bipolar disorders have a higher prevalence of psychiatric recurrences. Furthermore, the greater the number of previous relapses (or the longer the duration and intensity of the disease), the higher the risk of future new future recurrences both in bipolar disorders and recurring depressions. An age of onset of bipolar disorders before 60 years and more than 5 in-hospital admissions increase the risk of recurrences. We originally compare the outcome of bipolar disorders in the elderly, to recurring depressions and single depressions. We confirm the fatal outcome of recurrences in bipolar disorders in old age. Bipolar disorders in the elderly should be considered as a real public health care problem: strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively throughout life.

Are serum lithium levels related to the polarity of recurrence in bipolar disorders?

The primary objective is to test whether the polarity of recurrence (depressive vs manic or mixed), is related to lithium levels. A total of 86 euthymic bipolar patients (DSM-IV) on lithium monotherapy were prospectively followed up for 2.5 years with regular monitoring of both lithium levels and psychopathology. The last lithium level during the free interval that preceded worsening of affective symptoms was related to polarity of symptoms. To account for effects of major confounders, results were corroborated by multivariate analysis. An intervention for manic or mixed symptomatology was required in 27 patients, whereas 22 patients were treated for depressive symptoms. Average lithium levels preceding reappearance of manic or mixed symptomatology were lower than levels preceding reappearance of depressive symptoms (0.53+/-0.13 vs 0.66+/-0.21 mmol/l, P=0.01). This result was confirmed using logistic regression analyses with type of index episode, diagnostic subtype and residual manic and depressive symptoms as covariates. The results indicate that manic or mixed recurrences might rather occur at lower lithium levels, whereas the depressive pole prevails in the higher range. If substantiated by further studies, this finding might indicate that higher lithium levels are needed to prevent manic episodes than to prevent depressive episodes.