States Of Bipolar Disorder Research Articles

Mood and metabolic consequences of sleep deprivation as a potential endophenotype’ in bipolar disorder

It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression–dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression–dejection and anger–hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression–dejection, anger–hostility, and confusion–bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first-degree relatives of patients with bipolar disorder.

Does "crisis-induced intermittency" explain bipolar disorder dynamics?

The brain presents a large number of spatially connected and interacting neurons and synapses that form many positive and negative feedback circuits. These complex networks in interaction with the environment have been experimentally demonstrated to produce temporally chaotic behavior which may be detected in recordings from individual nerve cells or neural ensembles (Korn and Faure, 2003). According to such paradigm, the brain could be considered as a complex system with chaos as its predominant dynamics. As a result, concepts of complex system and chaos theory could be applied to the studies of normal and abnormal brain functions. One of the fundamental features of some complex systems is “multistability,” which can be understood as the coexistence of several interacting attractors (Chian et al., 2006). These interactions results in various complex behaviors in the long term dynamics of the system. Previous studies in several research areas, including neuroscience, have already reported the existence of multistability in natural systems (Chian et al., 2006; Goldbeter, 2011; Rabinovich et al., 2012). From the perspective of chaos theory, irregular alternation between episodes of various forms of chaotic or periodic behaviors is known as “intermittency” (Tanaka et al., 2005; Chian et al., 2006). In a “global bifurcation,” an “attractor-merging crisis” could yield to intermittent behavior. This crisis occurs through the collision of two or more attractors with the boundaries of the basin of the attraction of other attractors (Tanaka et al., 2005; Chian et al., 2006). In this case, by crossing the boundary, the trajectory of the system would be attracted by the other attractor. Such trajectory would then, remain there until another crossing which may lead to a returning to the first attractor. Chaotic intermittency has been reported in circuit oscillators, economic variables, non-periodic associative dynamics in chaotic neural networks as well as in psychiatric disorders like obsessive–compulsive disorder (Tanaka et al., 2005; Chian et al., 2006; Rabinovich and Varona, 2011). However, we believe that such concept also could be applied to mood variation pattern in bipolar disorder. According to physiological studies, neuroplastic variations may be the underlying mechanism which explain the misregulation of the main circuits involved in the emotional processing (Kandel et al., 2000; Berns and Nemeroff, 2003). This emotional dysregulation is somatically represented as irregular mood swings. Therefore, we believe that the clinical course of bipolar disorder, which is characterized by repeated erratic cycles of mania, depression and episodes of randomly appeared chaotic transitional states (Gottschalk et al., 1995; Berns and Nemeroff, 2003; Rabinovich et al., 2012), may also be understood based on the concept of chaotic intermittency. Manic, depressive and transitional states could be considered as stable or unstable attractors of a dynamical system through which the mood trajectory moves. Therefore, such accidental and abrupt changes of the mood state in bipolar disorder can result from the collision of the initial mood trajectory with the boundary of the basin of the attraction of the another mood attractors. According to chaos theory, this intermittent behavioral pattern could be considered as “crisis-induced intermittency.” Following such viewpoint, in healthy subjects, there would be only one “strange attractor” related to the mood states. Time series of such strange attractor represents both positive and negative emotions, unpredictably and in response to internal (for example thought, attention and memory) or external (environment) stimulus. In a bipolar person, however, initial emotional trigger of disease results in a type of “exterior crisis” in the system, in which the destruction of strange attractor is accompanied with formation of two abnormal attractors (mania and depression) and chaotic transients between them. In order to model such scenario, models of chaotic systems which demonstrate various kind of crisis by changing their parameters (such as “forced Duffing” oscillator and “Ikeda” iterated map), could be utilized to characterize the basic features of human emotional states, when they are presenting multistable and intermittent behaviors, as in the case of bipolar disorder. In order to provide a deeper insight in to such dynamics, we represent the time series of forced Duffing oscillator in its crisis-induced intermittent mode in Figure ​Figure1A1A and an example of temporal pattern of self-rated mood records (life charts) in a person with bipolar disorder in Figure ​Figure1B.1B. The proposed theoretical model would be useful in order to predict the evolution of such emotional states in bipolar disorder and to investigate the effects of psychopharmacological therapies. The experimental data for such investigations would most likely come from psychological tests, life chart recordings, or functional studies, such as EEG, fMRI, or PET-scan. Figure 1 (A) Example of crisis induced intermittency in the forced Duffing oscillator. (B) Example of temporal pattern of mood variation in a patient with bipolar disorder (Tretter et al., 2011).

Visual context processing in bipolar disorder: a comparison with schizophrenia

Anomalous perception has been investigated extensively in schizophrenia, but it is unclear whether these impairments are specific to schizophrenia or extend to other psychotic disorders. Recent studies of visual context processing in schizophrenia (Tibber et al., 2013; Yang et al., 2013) point to circumscribed, task-specific abnormalities. Here we examined visual contextual processing across a comprehensive set of visual tasks in individuals with bipolar disorder and compared their performance with that of our previously published results from schizophrenia and healthy participants tested on those same tasks. We quantified the degree to which the surrounding visual context alters a center stimulus' appearance for brightness, size, contrast, orientation and motion. Across these tasks, healthy participants showed robust contextual effects, as indicated by pronounced misperceptions of the center stimuli. Participants with bipolar disorder showed contextual effects similar in magnitude to those found in healthy participants on all tasks. This result differs from what we found in schizophrenia participants (Yang et al., 2013) who showed weakened contextual modulations of contrast but intact contextual modulations of perceived luminance and size. Yet in schizophrenia participants, the magnitude of the contrast illusion did not correlate with symptom measures. Performance on the contrast task by the bipolar disorder group also could not be distinguished from that of the schizophrenia group, and this may be attributed to the result that bipolar patients who presented with greater manic symptoms showed weaker contrast modulation. Thus, contrast gain control may be modulated by clinical state in bipolar disorder. Stronger motion and orientation context effects correlated with worse clinical symptoms across both patient groups and especially in schizophrenia participants. These results highlight the complexity of visual context processing in schizophrenia and bipolar disorder.

Impaired cognition in bipolar I disorder: The roles of the serotonin transporter and brain-derived neurotrophic factor

Studies have proposed that cognitive deficits are present in a variety of mood states in bipolar disorder (BD). The goal of this study was to find the cognitive deficits in euthymic BD patients and to further explore possible underlying mechanisms of the deficits. Thirty-three healthy controls (HCs) and twenty-three euthymic BD type I patients were recruited. Single photon emission computed tomography (SPECT) with (123)I-ADAM was used to image the serotonin transporter (SERT). Ten milliliters of venous blood was drawn for the measurement of brain derived neurotrophic factor (BDNF). Cognitive functions were tested included attention, memory, and executive function. We found that the SERT availability in both the midbrain and striatal regions was decreased in the BD patients compared with the HCs; however, the BDNF were not different between the two groups. There was no correlation between the SERT availability and the BDNF. Interestingly, there were statistically significant differences in sub-items of the facial memory test and the Wisconsin Card Sorting Test between the BD patients and the HCs, which showed that there was a cognitive deficit in the BD patients. However, the overall deficits in cognition were not significantly correlated with the SERT availability or the BDNF. The effect of medications on cognitive function and BDNF should be considered. We replicated previous findings that showed cognitive deficits in euthymic BD patients. However, the underlying mechanism of cognitive deficits in euthymic BD patients cannot be entirely explained by SERT and BDNF.

The Highs and Lows of Amygdala Reactivity in Bipolar Disorders

The Highs and Lows of Amygdala Reactivity in Bipolar Disorders

Changes in saccadic eye movement (SEM) and quantitative EEG parameter in bipolar patients

BackgroundThere is increasing evidence that neurocognitive dysfunction is associated with the different states in Bipolar Disorder. Gamma coherence is strongly related to cognitive processes and cortico-cortical communication. This paper aims at shedding light on the relationship between cortical gamma coherence within bipolar patients and a control group during a prosaccadic attention task. We hypothesized that gamma coherence oscillations act as a main neural mechanism underlying information processing which changes in bipolar patients. MethodThirty-two (12 healthy controls and 20 bipolar patients) subjects were enrolled in this study. The subjects performed a prosaccadic attention task while their brain activity pattern was recorded using quantitative electroencephalography (20 channels). ResultsWe observed that the maniac group presented lower saccade latency when compared to depression and control groups. The main finding was a greater gamma coherence for control group in the right hemisphere of both frontal and motor cortices caused by the execution of a prosaccadic attention task. LimitationsThe findings need to be confirmed in larger samples and in bipolar patients before start the pharmacological treatment. ConclusionsOur findings suggest a disrupted connection of the brain's entire functioning of maniac patients and represent a deregulation in cortical inhibitory mechanism. Thus, our results reinforce our hypothesis that greater gamma coherence in the right and left frontal cortices for the maniac group produces a “noise” during information processing and highlights that gamma coherence might be a biomarker for cognitive dysfunction during the manic state.

Discriminating primary clinical states in bipolar disorder with a comprehensive symptom scale

We assessed the spectrum and severity of bipolar symptoms that differentiated bipolar disorder (BD) clinical states, employing the Bipolar Inventory of Symptoms Scale (BISS) which provides a broader item range of traditional depression and mania rating scales. We addressed symptoms differentiating mixed states from depression or mania/hypomania. One hundred and sixteen subjects who met DSM-IV-TR criteria for BD and were currently in a depressed, manic/hypomanic, mixed episode, or recovered state were interviewed using the BISS. A subset of manic items differed between mixed episodes and mania/hypomania or depression. Most anxiety items were more severe in mixed subjects. BISS Depression and Manic subscales differentiated episodes from recovered status. The majority of depression and manic symptoms differentiated mood states in the predicted direction. Mixed episodes had overall greater mood severity than manic/hypomanic episodes or depressed episodes. These results indicate that a small subset of symptoms, several of which are absent in DSM-IV-TR criteria and traditional rating scales for bipolar studies, aid in distinguishing mixed episodes from depressive or manic/hypomanic episodes. The results also support the utility of a comprehensive BD symptom scale in distinguishing primary clinical states of BD.

Emotional hyperreactivity as a core dimension of manic and mixed states

Despite its obvious importance in mood disorders, characterization of emotional reactivity has been neglected in bipolar disorders. Concerning manic states and the current classification, the main criterion is the presence of an elevated or expansive mood. In contrast to this characteristic and often prolonged mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli. The goal of this study was to assess the intensity of emotional responses triggered by viewing slides in bipolar patients with manic or mixed states. Our hypothesis was that all emotional responses are exacerbated, whatever the valence of the stimuli. We compared 33 patients with manic or mixed states with 33 matched euthymic patients and 33 healthy control subjects. Arousal and attribution of valence were assessed while subjects viewed slides taken from the International Affective Picture System (positive, neutral and negative slides). Patients with manic or mixed states reported a higher arousal when viewing all types of slides in comparison with the other groups. Concerning attribution of valence, patients with manic or mixed states assessed neutral slides as more pleasant. When bipolar patients with manic and mixed states are placed in front of positive, neutral and negative slides, the slides trigger a higher intensity of emotions, whatever the valence of the emotional stimuli. These results strengthen the importance of emotional hyperreactivity as a core dimension in manic and mixed states in bipolar disorder.

Amygdala activity and prefrontal cortex–amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder

Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Thirty-one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block-design emotion processing task requiring color-labeling of a color flash superimposed on a task-irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top-down) and following (bottom-up) activity between the PFC and the left and right amygdalae. Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted-BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed-BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted-BD and depressed-BD subjects. EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala-PFC circuitry, supporting implicit emotion processing between remitted-BD and depressed-BD subjects, which may underlie changes from remission to depression in BD.

Add-on Lamotrigine Treatment for Subsyndromal Depression after Manic or Mixed States in Bipolar Disorder Improved the Quality of Life

Two cases of patients experienced subsyndromal depression after manic or mixed hypomanic and depressive episodes due to bipolar I (case 1) and II (case 2) disorders prior to the use of lamotrigine. Case 1 showed episodes of mood switching induced by antidepressants and seasonal mood instability. Case 2 showed hippocampal atrophy and a persistent dull headache that preceded the use of lamotrigine. Both were successfully treated with add-on lamotrigine therapy, and the dull headache was effectively treated with olanzapine. Both patients improved in social activity and work performance after these add-on treatments. Thus, add-on treatment with lamotrigine alone or in combination with olanzapine was an effective strategy to improve the quality of life in bipolar depression. Subsyndromal depression that present after the disappearance of the manic or mixed state was suggested to be practical indication for the use of lamotrigine.

Normal amygdala activation but deficient ventrolateral prefrontal activation in adults with bipolar disorder during euthymia

Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vlPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest.

Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder

Objective:Asenapine is approved for acute manic and mixed states in bipolar disorder. The objective is to review the efficacy of asenapine in bipolar disorder, with a particular focus on acceptability and adherence to treatment.Methods:Five clinical trials were conducted in bipolar disorder manic or mixed states: two 3-week trials (n = 976) comparing asenapine to placebo, a 9-week extension (n = 504), and a 40-week extension (n = 107). One trial was conducted comparing asenapine to placebo (n = 326) as adjunctive therapy for subjects with an incomplete response to lithium or valproate. All trials were conducted in the USA and internationally.Results:Asenapine was found to be efficacious for manic and mixed states in bipolar disorder compared with placebo control, and compares equally well to olanzapine on efficacy measures after 3 weeks of treatment. Asenapine was not found to be efficacious for depression symptoms. Common asenapine side effects in the 40-week extension trial were sedation, insomnia, and dizziness, and 31% reported clinically significant weight gain, compared with 55% reporting clinically significant weight gain with olanzapine. Additionally, 18% had clinically significant changes in fasting blood glucose levels compared to 22% of those on olanzapine. In terms of patient acceptability, one concern may be sublingual administration requiring no liquids or food for 10 minutes after dosing and a twice-daily regimen. Suggestions about addressing barriers to adherence and acceptability are provided.Conclusion:Asenapine is a promising new medication in bipolar disorder. Asenapine in the long-term has a more favorable weight gain profile compared to olanzapine. No benefit was seen for depression symptoms, a major patient-reported concern. Some side effects do not remit after the short-term trials in at least 10% of patients.

P01-231 - Emotional hyper-reactivity in normothymic bipolar patients

EUthymic states in bipolar disorders are generally considered to be devoid of severe symptoms. However, bipolar patients present subsyndromal symptoms for half of their life, and often have comorbid psychiatric disorders. If we go beyond the concept of temperamental features, can we identify certain emotional characteristics distinguishing normothymic bipolar patients from normal controls? The aim of this study was to assess the emotional reactivity of normothymic bipolar patients, comparing such patients with a normal control group during an experimental mood induction procedure.We evaluated the subjective emotional reactivity of 145 subjects (90 control subjects and 55 normothymic bipolar patients), using an emotional induction method based on the viewing of a set of slides (6 positive, 6 negative, 6 neutral) extracted from International Affective Picture System. Subjective valence and arousal were recorded with the Self Assessment Manikin.We also recorded startle reflexes.Normothymic bipolar patients and normal controls assessed valence and arousal similarly for positive and negative images. However, neutral images were considered more pleasant, and induced a higher level of arousal, in normothymic bipolar patients than in control subjects. Neutral pictures also triggered a stronger startle reflex in normothymic bipolar patients compared to controls.Normothymic bipolar patients displayed emotional hyper-reactivity, mostly evidenced in neutral situations. This feature may be linked to emotional dysregulation and is a potential endophenotype and or a risk factor for bipolar disorders. This trait may be responsible for vulnerability to minor stressful events in everyday life. These findings have potential implications for the daily management.

P01-202-Assessement of relationship between affective temperaments, trait impusivity and emotional response inhibition in euthymic state of bipolar disorder

IntroductionSeveral cognitive and behavioural disturbances persist in interepisodic bipolar disorder (BD). Affective temperaments may influence impairments as they contribute to the predisposition to BD and may share a common neurobiological basis with elevated trait impulsivity.AimsWe aimed to assess a relationship between temperamental traits and impulsivity as a trait and state dependent behaviour among euthymic bipolar outpatients and healthy volunteers.Methods38 euthymic bipolar outpatients and 24 healthy volunteers completed TEMPS-A and BIS-11. Computerised picture- based affective go/no-go task was applied to examine emotional response inhibition as an indicator of state dependent impulsivity.ResultsClinical group scored significantly higher than healthy volunteers on trait impulsivity and affective temperaments scales, and displayed poorer control of emotional response inhibition (Table 1). Correlation patterns were similar in both groups, with strong associations between the majority of affective temperaments and trait impulsivity components, while correlations between state dependent impulsivity measures appeared weak.ConclusionsDuring euthymia, distinctive temperament profile, elevated trait impulsivity and impaired emotional inhibition, prevailed among bipolar outpatients. This is consistent with data suggesting persistent abnormalities within specific areas of the prefrontal cortex and limbic structures which may underlie the emotional, cognitive and behavioural disturbances observed in all phases of BD.

Functional Impairment and Disability across Mood States in Bipolar Disorder

Background Bipolar disorder (BD) represents a chronic and recurrent illness that can lead to severe disruptions in family, social, and occupational functioning. The severity of mood symptomatology has been associated with functional impairment in this population. However, the majority of studies have assessed global functioning without considering specific domains. The main objective of the current study was to assess specific life domains of functioning as well as the overall functioning in patients with BD across different mood states ([hypo] mania, depression, or euthymia) compared with healthy controls by the means of a standardized scale validated for BD. Methods The sample included 131 subjects with BD (68 in remission, 31 hypo [manic], and 32 depressed) and 61 healthy controls. The Functioning Assessment Short Test was used to assess overall and multiple areas of functional impairment (autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time). Results The results showed significant intergroup differences; depressed patients had the lowest functioning (48.03 ± 12.38) followed by (hypo) manic patients (39.81 ± 13.99). The euthymic group showed least impairment in functioning compared with the depression and (hypo) mania groups (11.76 ± 12.73) but still displayed significant impairment when compared with the healthy control group (5.93 ± 4.43). Conclusions This study indicates that depressive symptoms are associated with greater negative impact on psychosocial functioning than (hypo) manic symptoms. Further deficits in functioning seem to persist during remission. The results highlight the importance of aggressively treating depression and mania and the need to develop psychosocial interventions targeting to improve functional outcomes.

Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder

Trait abnormalities in bipolar disorder (BD) within the ventral prefrontal cortex (vPFC) and the amygdala suggest dysfunction in their connectivity. This study employed low frequency resting state functional magnetic resonance imaging (LFRS-fMRI) to analyze functional connectivity between the vPFC and the amygdala in BD. LFRS-fMRI identified a negative correlation in vPFC–amygdala activity, and the magnitude of this correlation was greater in healthy participants than in subjects with BD. Additionally, whole-brain analysis revealed higher correlations between left and right vPFC in BD, as well as with ventral striatum.

Subsyndromal states in bipolar disorder

Background:Despite adequate treatment, patients with bipolar disorder suffer from subsyndromal symptoms. This study has been done to see the association of subsyndromal symptoms with age of onset, duration of illness, duration of episodes, and number of episodes.Aims:To know the prevalence of subsyndromal symptoms and their relationship with age of onset, total duration of illness, number of episodes, and duration of episodes in patients with bipolar disorder in remission.Materials and Methods:The study was cross sectional and hospital based. One hundred patients, aged between 18 and 65 years, diagnosed as bipolar disorder according to Research Diagnostic Criteria of ICD-10, and with good compliance with the prophylactic medications, score of ≤5 on Beck’s Mania Rating Scale (BMRS) and score ≤8 on Hamilton Depression Rating Scale (HDRS) were recruited by the purposive sampling method. Descriptive statistics were used to describe various sample characteristics. Group differences for categorical variables were examined with the chi-square test, whereas an independent ‘t’ test was used for continuous variables.Results:The most common manic symptom was a decrease in sleep (49%), followed by an increase in verbal activity (39%), hostility (37%), and increase in motor activity (33.33%). The subsyndromal manic group had a lower age of onset (58.8%), males (82.4%), unemployed (23.5%), educated (80.4%). There was no significant difference between with and without subsyndromal mania groups with respect to age, age of onset, duration of illness, number of episode, and average duration of episode.Conclusion:Subsyndromal manic symptoms are prevalent and have no relationship with current age, age of onset of illness, duration of illness, number of episode, and average duration of illness in patient with bipolar disorder in remission.

A novel scale for measuring mixed states in bipolar disorder

Conventional descriptions of bipolar disorder tend to treat the mixed state as something of an afterthought. There is no scale that specifically measures the phenomena of the mixed state. This study aimed to test a novel scale for mixed state in a clinical and community population of bipolar patients. The scale included clinically relevant symptoms of both mania and depression in a bivariate scale. Recovered respondents were asked to recall their last manic episode. The scale allowed endorsement of one or more of the manic and depressive symptoms. Internal consistency analyses were carried out using Cronbach alpha. Factor analysis was carried out using a standard Principal Components Analysis followed by Varimax Rotation. A confirmatory factor analytic method was used to validate the scale structure in a representative clinical sample. The reliability analysis gave a Cronbach alpha value of 0.950, with a range of corrected-item-total-scale correlations from 0.546 (weight change) to 0.830 (mood). The factor analysis revealed a two-factor solution for the manic and depressed items which accounted for 61.2% of the variance in the data. Factor 1 represented physical activity, verbal activity, thought processes and mood. Factor 2 represented eating habits, weight change, passage of time and pain sensitivity. This novel scale appears to capture the key features of mixed states. The two-factor solution fits well with previous models of bipolar disorder and concurs with the view that mixed states may be more than the sum of their parts.

Pharmacologic treatment of rapid cycling and mixed states in bipolar disorder: an argument for the use of lithium

Lithium has long been considered as less than ideal in the management of rapid cycling and mixed states in bipolar disorder. However, these forms of bipolarity represent a generally more difficult phase of the illness to treat with any medication. Increasing knowledge about lithium's other beneficial effects, including protection against suicide and neuromodulatory effects which may protect the brain, make it a first-line treatment for any form of bipolar disorder. As newer therapies become available or receive further exploration, we should look to the past and re-embrace lithium as a core therapeutic modality for bipolarity as we move forward in the field, particularly for forms of the disorder such as rapid cycling and mixed states, historically thought to be more treatment resistant.

Réactivité émotionnelle chez les patients bipolaires en phase de normothymie

Euthymic states in bipolar disorders are usually considered to be lacking serious psychiatric disorders. Moreover, recent results prove the need to take an interest in a potential emotional dysregulation during these intercrisis periods. Therefore, it seems relevant not only to focus on the emotions tonality (sadness/euphoria) felt by patients, but also on the intensity of their emotional background. Several reasons argue for a disturbance of emotional reactivity in euthymic bipolar patients. First, most bipolar patients spontaneously claim they have a higher sensitivity than average, which may lead to extreme emotional reactions, even during intercrisis periods. Secondly, the emotional reactivity is a way to raise the question of the bipolar patients' vulnerability to stress in euthymic periods. Several studies have shown the impact of stressful life events on the rate of relapse into bipolar disorders. The aim of this study is to examine the emotional reactivity of euthymic bipolar patients in comparison with a control group, using a test of emotional induction. Our hypothesis is that euthymic bipolar patients have a higher emotional reactivity than controls. One hundred and forty-five subjects were recruited: 90 controls and 55 euthymic bipolar patients. The patients were interviewed by a trained psychologist using the French version of the DIGS providing DSM-IV diagnosis. The euthymic state was confirmed with both MADRS (score<12) and Bech's Manic Scale (score<4). The subjective emotional reactivity of the subjects was assessed using a method of emotional induction, based on viewing a set of 18 (positive, negative or neutral) pictures. The subjects have to appreciate the valence (pleasant, neutral or unpleasant thoughts) and assess the arousal (degree of emotion triggered by each picture). On average, euthymic bipolar patients report the same valence and arousal to positive (F [1.143]=0.18, p=0.68) and negative (F [1.143]=0.52, p=0.47) pictures as control subjects. Neutral pictures, however, were considered more pleasant and moving by euthymic bipolar patients than by control subjects (F [1.143]=8.40, p=0.004). Euthymic bipolar patients seem to present an emotional hyperactivity which occurs especially in neutral situations. These results partly corroborate outcomes of other authors, while providing a new methodology through the emotional induction test. The highlight of emotional hyperreactivity during intercrisis periods allows us to understand differently the topic of specific vulnerability to stress of bipolar patients. This hypersensitivity could lead to thymic decompensations and could be linked with an emotional dysregulation, potential endophenotype of the bipolar pathology. Beyond the interest in understanding the physiopathology of the bipolar disorder, it could be associated with several clinical applications as well as in the psychoeducational field and in the screening of the individual risk within the family of bipolar subjects.