States Of Bipolar Disorder Research Articles

The use of triiodothyronine as an augmentation agent in treatment-resistant bipolar II and bipolar disorder NOS

Background Thyroid hormone plays a role in both serotonin and catecholamine functions in the brain, and has been linked to abnormal mood states in bipolar disorder. Unlike most studies which have included only patients with bipolar I, this study evaluated triiodothyronine (T3) as an augmentation agent for treatment-resistant depression in patients with bipolar II and bipolar disorder NOS. Methods This study was a retrospective chart review of patients treated in a private clinic between 2002 and 2006. The charts of 125 patients with bipolar II disorder and 34 patients with bipolar disorder NOS were reviewed. Results Patients had been unsuccessfully treated with an average of 14 other medications before starting T3. At an average dose of 90.4 mcg (range 13 mcg–188 mcg) the medication was well tolerated. None of the patients experienced a switch into hypomania, and only 16 discontinued due to side effects. Improvement was experienced by 84%, and 33% experienced full remission. Limitations The limitations are those associated with the retrospective chart review design. Conclusions A high percentage of bipolar II and bipolar NOS patients with treatment resistant depression improved on T3. Despite the use of higher than usual doses in many of the patients, the medication was well tolerated. Augmentation with supraphysiologic doses of T3 should be considered in cases of treatment resistant bipolar depression.

Brain GABA levels in patients with bipolar disorder

Purpose A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients. General methods We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls. Findings There were no significant differences in GABA, glutamate or glutamine between patients and controls. Conclusions Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder.

Emotional hyper‐reactivity in normothymic bipolar patients

Normothymic states in bipolar disorders are generally considered to be devoid of severe symptoms. However, bipolar patients present subsyndromal symptoms for half of their lives, 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? We previously showed, using self-completed questionnaires, that normothymic bipolar patients display higher levels of emotional lability and intensity than 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 18 pictures (6 positive, 6 negative, 6 neutral) extracted from the International Affective Picture System. Subjective valence and arousal were recorded with the Self-Assessment Manikin. We also recorded startle reflexes, triggered by a tone occurring during the viewing of two-thirds of the pictures. We controlled for confounding factors, such as concurrent treatments, in all analyses. Normothymic bipolar patients and normal controls assessed valence and arousal similarly for positive and negative images. However, neutral images were considered more pleasant [F(1,143) = 8.4; p = 0.004] and induced a higher level of arousal [F(1,143) = 12.3; p = 0.001] in normothymic bipolar patients than in control subjects. Neutral pictures also triggered a stronger startle reflex in normothymic bipolar patients compared to controls [F(3,123) = 3.1; p = 0.03]. 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 of bipolar disorder between crises.

A study on characteristics of cognitive function of bipolar disorder

Objective To explore the patterns of cognitive performance across different clinical states of bipolar disorder(BPD).Methods 8 neuropsychological tests (17 items) which examine attention,verbal learning and memory,visual memory and executive function were given to 30 depressed BPD ,30 manic BPD ,30 remitted BPD and 34 normal controls.The difference of cognitive functions between the four groups were compared using multivariate analysis of variance (MANOVA).Results Acute patients with BPD showed dysfunction in almost all neuropsychological tests compared with controls [ the score of WCST categories of manic BPD,depressed BPD,remired BPD and normal controls was( 1.58 ±0.90),( 1.89± 1.56),(2.44 ± 1.42),(4.90 ± 1.73 ) respective-ly.The score of immediately logical memory was (10.68±3.92),(10.00±3.80) ,(12.11±3.72),(15.80±4.21) respectively] (P<0.05,P<0.01).The remitted patients showed deficits in attention,verbal learning and memory,executive function tasks in relation to controls (P<0.05,P<0.01).Conclusion There were general cognitive deficits in acute patients with BPD,and some of these deficits may persists in remission state. Key words: Bipolar disorder; Cognitive function; Nueropsychology tests

Construction and validation of a dimensional scale exploring mood disorders: MAThyS (Multidimensional Assessment of Thymic States)

BackgroundThe boundaries between mood states in bipolar disorders are not clear when they are associated with mixed characteristics. This leads to some confusion to define appropriate therapeutic strategies. A dimensional approach might help to better define bipolar moods states and more specifically those with mixed features.Therefore, we proposed a new tool based on a dimensional approach, built with a priori five sub-scales and focus on emotional reactivity rather than exclusively on mood tonality. This study was designed to validate this MAThyS Scale (Multidimensional Assessment of Thymic States).MethodsOne hundred and ninety six subjects were included: 44 controls and 152 bipolar patients in various states: euthymic, manic or depressed. The MAThyS is a visual analogic scale consisting of 20 items. These items corresponded to five quantitative dimensions ranging from inhibition to excitation: emotional reactivity, thought processes, psychomotor function, motivation and sensory perception. They were selected as they represent clinically relevant quantitative traits.ResultsConfirmatory analyses demonstrated a good validity for this scale, and a good internal consistency (Cronbach's alpha coefficient = 0.95). The MathyS scale is moderately correlated of both the MADRS scale (depressive score; r = -0.45) and the MAS scale (manic score; r = 0.56).When considering the Kaiser-Guttman rule and the scree plot, our model of 5 factors seems to be valid. The four first factors have an eigenvalue greater than 1.0 and the eigenvalue of the factor five is 0.97. In the scree plot, the "elbow", or the point at which the curve bends, indicates 5 factors to extract. This 5 factors structure explains 68 per cent of variance.ConclusionThe characterisation of bipolar mood states based on a global score assessing inhibition/activation process (total score of the MATHyS) associated with descriptive analysis on sub-scores such as emotional reactivity (rather than the classical opposition euphoria/sadness) can be useful to better understand the broad spectrum of mixed states.

Treating Depressive Mixed States in Bipolar Disorders

Although not recognized as a diagnostic entity in the DSM-IV-TR, mixed depression is a common clinical presentation. To treat depressive mixed states, clinicians in both Europe and the United States have developed valuable, yet different, therapeutic strategies. For example, the European model focuses on resolving patients' hypomanic symptoms, while the American model treats patients in depressive mixed episodes similarly to those who have bipolar II disorder. Common treatment practices between the 2 paradigms include the art of adopting pharmacotherapeutic regimens that are tailored to the needs of each patient and frequent evaluation of the patient's progress.

Diagnosing Depressive Mixed States in Bipolar Disorders

The presence of depressive mixed states among patients originally diagnosed with unipolar depression suggests that these patients may actually fall along the bipolar spectrum, which has significant treatment implications. To accurately detect mixed depression, physicians should systematically inquire about the presence of manic and hypomanic symptoms in a formal, structured manner when evaluating a depressed patient. This includes specifically asking patients about symptoms of irritability, racing or crowded thoughts, talkativeness, and psychomotor agitation. Swift and accurate diagnosis of depressive mixed states is essential to alleviating symptoms and improving outcomes for patients with bipolar disorders.

Diagnostic Dilemmas and Clinical Correlates of Mixed States in Bipolar Disorder

Patients with bipolar disorder frequently have varying degrees of mixed states rather than pure episodic manic and depressive episodes. However, DSM-IV-TR and ICD-10 criteria do not fully account for patients' varying presentations; currently, there is no consensus on whether mixed states is a distinct, categorically different type of mania or whether it is a transitional state between depression and mania. Inconsistent diagnostic criteria can be problematic for clinicians when treating patients.

Investigation of serum high-sensitive C-reactive protein levels across all mood states in bipolar disorder

There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.

Electroconvulsive therapy in the treatment of mixed states in bipolar disorder

Introduction. Mixed bipolar states are not infrequent and may be extremely difficult to treat. Lithium, anticonvulsants including valproate and carbamazepine, and antipsychotics such as olanzapine, ziprasidone, and aripiprazole have been reported to be at least partially effective in controlled clinical trials, but many patients do not respond to pharmacological approaches. Electroconvulsive therapy has been tested to be efficacious for the treatment of both manic and depressive episodes, but much less evidence is available with regards to mixed states. The aim of the review was to report the available evidence for the use of electroconvulsive therapy in mixed bipolar states.Methods. A systematic review of the literature on treatment of mixed states, focused on electroconvulsive therapy, was made, beginning in August 1992 and ending in March 2007. The key words were “electroconvulsive therapy” and “mixed bipolar”.Results. Only three studies met the required quality criteria and were included. This literature suggests that ECT is an effective, safe, and probably underutilized treatment of mixed states. Recent technical developments have made ECT more friendly, tolerable, and safe. Potential alternatives, such as vagus nerve stimulation, deep brain stimulation, or transcranial stimulation, are still far to be proved as effective as ECT.

Antiepileptic Drugs and Mood Stability

This paper will discuss different definitions of the term "mood stabilizer" and highlight in detail the antiepileptic drugs carbamazepine, valproate and lamotrigine with respect to their relative strengths in stabilizing mood in bipolar patients. These drugs are heterogeneous in their mechanisms of action and in their efficacy to stabilize patients with epilepsy and the various mood states in bipolar disorder. Lamotrigine has obtained approval in several countries for the indication of preventing bipolar depressive episodes, which raises the question of differential efficacy of other antiepileptic drugs as mood stabilizers in the prevention of either depressive or hypo-/manic episodes. A Medline Search to 2006 was conducted for controlled acute and maintenance studies of the three scientifically and clinically most established antiepileptic drugs carbamazepine, valproate and lamotrigine. The medications discussed in this review only partly fulfill definitions of a mood stabilizer, and we suggest that future research should focus on combined treatment strategies.

Affektive Mischzustände bei Bipolaren Störungen: ein Überblick

Affective mixed states in bipolar disorders are a current matter of scientific debate and represent a complex clinical picture with coexisting manic and depressive symptoms. Treatment of mixed states is regarded as an important challenge. As diagnostic uncertainties complicate systematic clinical evaluations of this patient group, generally accepted clinical treatment guidelines are lacking yet. In this review the significance as well as the problems and risks of new treatment options are discussed.

Bipolar Disorder: Imaging State Versus Trait

Bipolar Disorder: Imaging State Versus Trait

Multiplicité des syndromes associant symptômes dépressifs et maniaques: nécessité d’une approche dimensionnelle

The heterogeneity of mood states in bipolar disorders leads to some confusion in diagnostic and therapeutic strategies. Apart from the classical syndromes characterizing euphoric mania and melancholic depression, recent literature has pointed to alternative mood states associating both manic and depressive symptoms. This resulted in the definition of various syndromes including mixed states, dysphoric mania, agitated depression and more recently the depressive mixed state. This consequently raises the question of the best therapeutic strategies. As the boundaries between the various states associating both depressive and manic symptoms have yet to be clarified, there is a need to further discuss whether dimensional rather than categorical approaches could help to further refine their definitions and define the best therapeutic strategies. As stated by Kraepelin, mood episodes in manic-depressive illness were defined according to three dimensions: mood, cognitive processes, and motor and motivational drive. Cognitive and motor processes were regarded as quantitative items whose alterations may correspond to either an increase or a decrease. The current definitions are far from this dimensional approach. Thus, the current diagnostic criteria make it difficult to define mixed states. Such poorly convincing diagnostic criteria may account for the description of many other states exhibiting both manic and depressive symptoms. A dimensional approach could be useful to define mood states in bipolar disorders. These dimensions should progressive, from inhibition to excitation. Because tonality affects is not a dimension, the emotional reactivity (hyper-reactivity versus hypo-reactivity) represents an additional dimension that would help characterize these states better.

Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls

To assess the relations between sustained attention as assessed by the Continuous Performance Test (CPT) and subgenual and dorsolateral prefrontal cortex metabolism in depressed patients with bipolar disorders and healthy controls. Cross-sectional case-control design. Cerebral metabolic rates were assessed with 18F-fluoro-deoxyglucose and positron emission tomography (PET) in the regions of interest defined on co-registered structural magnetic resonance images in eight medication-free, depressed bipolar disorder patients and 27 healthy control participants. PET scans were obtained in a resting state and the CPT was administered within 1 week of the PET scan. Although there were no statistically significant differences in performance on the CPT or in cerebral metabolism between the two groups, our analyses revealed differential relations between the CPT and metabolism across the groups. Decreased subgenual prefrontal metabolism was associated with slower hit rate reaction time and more omission errors in the bipolar group, but not the control group. Decreased dorsolateral prefrontal metabolism in the bipolar group, but not the control group, was associated with more commission errors. This study extends previous neuroimaging findings of structural and functional relevance of the prefrontal region with attention to include depressed states in bipolar disorder. The results are consistent with interpretations that decreased prefrontal activity may represent failure to activate some areas of inhibitory control. Decreasing subgenual prefrontal cortex metabolism appears to relate to decreased attention whereas the decreased dorsolateral prefrontal cortex metabolism relates more to decreased inhibitory control.

Comparisons of perceived quality of life across clinical states in bipolar disorder: data from the first 2000 Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) participants

Background Evidence indicates that quality of life is subnormal in patients with bipolar disorder and that it differs across mood states. However, the pattern of specific deficits has not been well studied, and the role of potential confounders has received no attention. Method We investigated the self-reported quality of life, Medical Outcomes Study 36-Item Short Form (SF-36), and Quality of Life Enjoyment and Satisfaction (QLESQ) at baseline across the clinical states of the first 2000 participants enrolled in Systematic Treatment Enhancement Program for Bipolar Disorder. Results Bivariate analyses indicated significant differences across mood state, with depressive symptoms predicting lower SF-36 mental and physical scores and QLESQ overall score. However, adjustment for relevant clinical and demographic variables erased the difference in the SF-36 physical score. Notably, covariate adjustment removed the apparently “supranormal” SF-36 mental and QLESQ scores among those with mania/hypomania compared with those euthymic. Conclusion Depressive symptoms are a strong predictor of quality of life, yet covariate adjustment has an impact as well. Clinically, this indicates the need for addressing these factors if quality of life is to be maximized. Such factors should also be taken into account in future naturalistic and clinical trials research on quality of life in bipolar disorder.

Impaired cognition and decision-making in bipolar depression but no ‘affective bias’ evident

Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.

Bipolar disorder and cognitive therapy: A commentary

This article comments on the three articles ( Leahy, 2005; Newman, 2005; and Reilly-Harrington & Knauz, 2005 ) that deal with the applications of cognitive therapy to treatment of bipolar disorder. They focus on the uses of cognitive therapy in treating three important facets of the special problems of bipolar patients: rapid cycling, severe depression/suicidality, and manic states. This article concludes its commentary with several open questions and ideas about the role of thought suppression and rebound processes in the cycling between depressive or euthymic and manic states in bipolar disorder.

Rapid mood switching and suicidality in familial bipolar disorder

Rapidly alternating or mixed mood states in bipolar disorder are associated with a particularly high risk for suicidal behavior. Are individuals with these patterns of illness more likely to develop suicidal intentions, or are they less able to resist them? This analysis examines the specific contribution of rapid switching and other variables to the relative likelihood of having or acting on self-reported suicidal thought and action, in a large group of individuals with bipolar disorder. The analysis included 1574 family members with bipolar disorder interviewed for a multi-site bipolar disorder genetic linkage study. Two models were tested, using the same set of demographic and clinical data points as independent variables. One model tested the influence of rapid switching and other variables on self-reported suicidal thought or action (i.e., suicidality), while the other tested the influences on suicidal action only among those who reported a history of suicidality. Over 75% of subjects had contemplated suicide and 38% reported a history of suicidal behavior. A history of rapid switching was associated with higher likelihood of a history of suicidality, as was panic disorder. Familial suicidal behavior, as well as drug abuse, increased the likelihood of suicidal action among suicidal individuals, but did not increase the likelihood of becoming suicidal. Female sex, early age at onset, and several demographic factors were associated with both facets of suicidality. Factors associated with high acuity of distress, such as panic attacks and unstable moods, appear to enhance the risk of suicidality in general. Factors that affected the threshold for action without increasing suicidality overall can also be seen as markers of impulsive decision-making. Of the two distinct kinds of suicidal risk, the latter - the likelihood of action given intent - appears to be the more familial.

Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder.

The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning. Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score > or = 17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score > or = 12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score < or = 8, and Young Mania Rating Scale score < or = 6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory. The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts. A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.