Arthur Kaladjian

Risk factors associated with lifetime suicide attempts in bipolar I patients: findings from a French National Cohort.

Risk factors that may be associated with suicide attempts in bipolar disorder are still a matter of debate. We compared demographic, illness course, clinical, and temperamental features of suicide attempters vs those of nonattempters in a large sample of bipolar I patients admitted for an index manic episode. One thousand ninety patients (attempters = 382, nonattempters = 708) were included in the study. Multivariate analysis evidenced 8 risk factors associated with lifetime suicide attempts as follows: multiple hospitalizations, depressive or mixed polarity of first episode, presence of stressful life events before illness onset, younger age at onset, no free intervals between episodes, female sex, higher number of previous episodes, and cyclothymic temperament. These characteristics may help identify subjects at risk for suicide attempt throughout the course of bipolar disorder. We finally propose to integrate such characteristics into a stress-diathesis model of suicidal behavior, adapted to bipolar patients.

Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort

Background: Despite numerous studies on the comorbidity of bipolar and anxiety disorders, there is no satisfactory psychopathological model for their overlap. Method: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode of bipolar I disorder were subtyped according to the presence or not of lifetime anxiety comorbidity and assessed for demographic, illness course, clinical, associated condition, temperament, and treatment characteristics. Results: Lifetime anxiety comorbidity, defined as presence of at least one anxiety disorder in lifetime, was found in 27.2% (n = 297) of the sample. Compared to patients without such a comorbidity (n = 793), those who had it experienced a higher number of mood episodes and suicide attempts in the previous year, more stressors, organic disorders and less free intervals; furthermore, they showed more temperaments with depressive features and complex treatment. At study entry, they also experienced manic episodes with higher levels of depression, psychosis and hostility. The following independent variables were associated with lifetime anxiety comorbidity: higher scores on the Montgomery-Åsberg Depression Rating Scale, depressive temperament, irritable temperament, higher scores on the Scale for the Assessment of Positive Symptoms, episodes without free intervals and at least one stressor before the index episode. Conclusions: Factors associated with lifetime anxiety comorbidity in bipolar I patients may be integrated into a comprehensive diathesis-stress model emphasizing the role of irritable temperament as a source of mood instability and stress, and interacting with other temperamental characteristics to trigger the outbreak of both anxiety and bipolar symptoms.

Characteristics and profiles of bipolar I patients according to age-at-onset: findings from an admixture analysis.

BACKGROUND Many studies have used admixture analysis to separate age-at-onset (AAO) subgroups in bipolar patients, but few have looked at the phenomenological characteristics of these subgroups, in order to find out phenotypic markers. METHODS Admixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 1082 consecutive DSM-IV bipolar I manic inpatients who were assessed for demographic, clinical, course of illness, comorbidity, and temperamental characteristics. RESULTS The model best fitting the observed distribution of AAO was a mixture of three Gaussian distributions. We could identify three AAO subgroups: early, intermediate, and late age-at-onset (EAO, IAO, and LAO, respectively). Patients in the EAO subgroup were more often single young males exhibiting severe mania with psychotic features, a subcontinuous course of illness with substance use and panic comorbidity, more suicide attempts, and temperamental components sharing hypomanic features. Patients with LAO showed a less severe picture with more depressive temperamental components, alcohol use and comorbid general medical conditions. A less typical phenotype was present in IAO patients. LIMITATIONS The following are the limitations of this study: retrospective design, and bias toward preferential enrollment of patients with manic predominant polarity. CONCLUSIONS This study confirms that bipolar I disorder can be subdivided into three subgroups based on AAO distribution and shows that patients from these subgroups differ in phenotypes.

Factors associated with rapid cycling in bipolar I manic patients: findings from a French national study.

INTRODUCTION Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness. METHODS From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or nonrapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics. RESULTS Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed. CONCLUSION Our findings may confirm previous descriptions, according to which rapid cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.

Remission from mania is associated with a decrease in amygdala activation during motor response inhibition.

OBJECTIVES Neuroimaging studies of bipolar disorder (BD) have provided evidence of brain functional abnormalities during both the states of mania and remission. However, the differences in brain function between these two states are still poorly known. In the current study, we aimed to use a longitudinal design to examine the functional changes associated with symptomatic remission from mania within the brain network underlying motor response inhibition. METHODS Using event-related functional magnetic resonance imaging (fMRI), 10 BD patients and 10 healthy subjects were imaged twice while performing a Go/NoGo task. Patients were in a manic state when they underwent the first scan and fully remitted during the second scan. A mixed-effect ANOVA was used to identify brain regions showing differences in activation change over time between the two groups. RESULTS The left amygdala was the only brain region to show a time-dependent change in activation that was significantly different between BD patients and healthy subjects. Further analyses revealed that this difference arose from the patient group, in which amygdala activation was decreased between mania and subsequent remission. CONCLUSIONS This finding suggests that a decrease in left amygdala responsiveness is a critical phenomenon associated with remission from mania. It emphasizes the relevance of longitudinal approaches for identifying neurofunctional modifications associated with mood changes in BD.

Self-assessment and characteristics of mixed depression in the French national EPIDEP study.

BACKGROUND Studies on mixed depression have been conducted so far on the basis of DSM-IV manic symptoms, i.e., a list of 7 symptoms which may provide limited information on the subsyndromal features associated with a full depressive episode. METHODS As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 102 (23.8%) were classified as mixed depressives (≥3 hypomanic symptoms), and 146 (34%) as pure depressives (0 hypomanic symptom), after exclusion of bipolar I patients; hypomanic symptoms were assessed with the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self assessment format. A narrower definition of mixed depression, resting on those MVAS-BP items referring to DSM-IV hypomanic symptoms was also tested, as a sensitivity analysis. RESULTS Compared to pure depressives, mixed depressive patients had more psychotic symptoms, atypical features and suicide attempts during their index episode; their illness course was characterized by early age at onset, frequent episodes, rapid cycling, and comorbidities. Mixed depressive patients were more frequently bipolar with a family history of bipolar disorder, alcohol abuse, and suicide. A dose-response relationship was found between intradepression hypomania and several clinical features, including temperament measures. The following independent variables were associated with mixed depression: hyperthymic temperament, cyclothymic temperament, irritable temperament, and alcohol abuse. Using the narrower definition of mixed depression missed risk factors such as suicidality and comorbidities. LIMITATIONS The following are the limitations of this study: retrospective design, recall bias, lack of sample homogeneity, no cross-validation of findings by hetero-evaluation of hypomanic symptoms. CONCLUSIONS EPIDEP data showed the feasibility and face validity of self-assessment of intradepressive hypomania. They replicated previous findings on the severity and high suicidal risk of mixed depression profile. They confirmed, for mixed depression, that mixed states occur when mood episodes are superimposed upon temperaments of opposite polarity. They finally suggested that a definition of mixed depression only based on DSM-IV-TR hypomanic symptoms may not allow to identify the most unstable subforms of the entity.

Stroop and emotional Stroop interference in unaffected relatives of patients with schizophrenic and bipolar disorders: distinct markers of vulnerability?

Reduced inhibition has been demonstrated in both schizophrenic and bipolar patients through the findings of increased interference on the Stroop Colour-Word Task (SCWT) and increased emotional interference on specific versions of the Emotional Stroop Task (EST). Despite previous findings of enhanced interference in unaffected relatives of schizophrenic and bipolar patients, it remains unclear whether interference might be a candidate endophenotype to both disorders. Moreover, data regarding emotional interference in unaffected relatives are critically lacking. In the present study, we aimed to compare unaffected relatives of patients with schizophrenia (SZ-rel, N = 30) and bipolar disorder (BD-rel, N= 30) with normal controls (N = 60) when performing the SCWT and an EST designed with neutral, depressive, paranoid and manic words. SZ-rel exhibited greater interference effect on both the SCWT and the EST as compared to either BD-rel or normal controls. BD-rel, and by contrast to SZ-rel and controls, showed increased emotional interference effect on the EST that was specifically associated to the disease-related words. The findings support the hypothesis of different markers of vulnerability to schizophrenic and bipolar disorders; impairment in cognitive inhibition could characterize high-risk individuals for schizophrenia whereas an emotional bias towards mood-related information could be a trait marker of bipolar disease.

Risks associated with gender differences in bipolar I disorder

BACKGROUND Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial. METHODS The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender. RESULTS Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (-), excessive alcohol use (+), cyclothymic temperament (-), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+). LIMITATIONS The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations. CONCLUSIONS Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.

Correlates of first-episode polarity in a French cohort of 1089 bipolar I disorder patients: Role of temperaments and triggering events

OBJECTIVES As only a few studies so far systematically reported on bipolar patients subtyped according to first-episode polarity, we took the opportunity of having at disposal a large sample of bipolar I patients to specify the characteristics of patients included in these subtypes, with a special focus on temperament and triggering events. METHODS A total of 1089 consecutive DSM-IV bipolar I manic inpatients were subtyped in manic onset (MO), depressive onset (DO) and mixed onset (MXO), and assessed for demographic, illness course, clinical, psychometric, comorbidity and temperament characteristics. RESULTS The main characteristics of MO patients were a hyperthymic temperamental predisposition, a first episode triggered by substance abuse and an illness course with pure, severe and psychotic mania. In comparison, DO patients had more depressive temperaments, a first episode triggered by stress and alcohol, an illness course with more episodes, cyclicity, suicide attempts, anxious comorbidity and residual symptoms. Although sharing characteristics with either MO or DO, MXO patients had more mixed episodes and cyclothymic temperament. LIMITATIONS The following are the limitations of this study: retrospective design, bias toward preferential enrolment of MO patients, and lack of information on the number and polarity of lifetime episodes. CONCLUSIONS Findings from this study tend to confirm most of the differences previously evidenced among patients subtyped according to first-episode polarity. Differences found in temperamental predisposition and illness onset triggering events are worth noting and may help target early preventive interventions as well as orientate the search for specific genetic risk factors.

Late‐onset Bipolar Illness: The Geriatric Bipolar Type VI

In parallel to considerable progress in understanding and treatment of bipolarity and despite growing interest in old age psychiatry, late‐onset bipolar illness (LOBI) has remained relatively understudied so far, probably in reason of its complexity. To update available data, a systematic review was conducted, focusing on the main issues addressed in literature in regard to this topic. In addition to data on epidemiology, clinical features and treatment, five main issues could be identified: LOBI as secondary disorder, LOBI as expression of a lower vulnerability to the disease, LOBI as subform of pseudodementia, LOBI as risk factor for developing dementia, and LOBI as bipolar type VI (bipolarity in the context of dementia like processes). Levels of available evidence were found to vary according to the addressed issue. Although the concept of bipolar type VI could be criticized for subsuming under one single heading all the four other issues, this concept may be of pragmatic value in helping clinicians to orientate both diagnosis process and treatment decisions. Among others, the question as to whether some forms of bipolar type VI could constitute a special risk factor for developing dementia deserves further investigation. More studies are also needed to better disentangle the effects of age at onset from those of age itself.