Multidimensional Assessment Of Thymic States Research Articles

Emotional hyper-reactivity and cardiometabolic risk in remitted bipolar patients: a machine learning approach.

Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. After adjustment, patients with emotional hyper-reactivity (n=306) had significantly higher levels of systolic and diastolic blood pressure (P<1.0×10-8 ), high-sensitivity C-reactive protein (P<1.0×10-8 ), fasting glucose (P<2.23×10-6 ), glycated hemoglobin (P=0.0008) and suicide attempts (P=1.4×10-8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide.

Emotional reactivity, functioning, and C-reactive protein alterations in remitted bipolar patients: Clinical relevance of a dimensional approach.

Inter-episode mood instability has increasingly been considered in bipolar disorder. This study aimed to investigate emotional reactivity as a major dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms and functional status. This study also aimed to investigate whether high-sensitivity C-reactive protein, a marker of low-grade inflammation, could be a biological marker of emotional dysregulation in bipolar disorder (BD). Cross-sectional study of 613 subjects who met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for BD recruited from the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort from 2009 to 2014. All patients had been in remission for at least 3 months before assessment. Patients were classified into three groups according to levels of emotional reactivity. Emotional reactivity was assessed by using the Multidimensional Assessment of Thymic States, and functional status was assessed by the Functioning Assessment Short Test. Clinical characteristics and blood sample were collected from all patients. In total, 415 (68%) patients had abnormal emotional reactivity. Independent of potential confounders, including age, gender and subthreshold mood symptoms, serum levels of high-sensitivity C-reactive protein were significantly higher in patients with emotional hyper-reactivity (median = 4.0 mg/L, interquartile range = 2.7-5.6), and with emotional hypo-reactivity (median = 3.0 mg/L, interquartile range = 1-4) compared with patients with normal emotional reactivity (median = 0.95 mg/L, interquartile range = 0.4-1.9, p < 0.001). Patients with emotional hyper-reactivity showed significant cognitive functioning impairment ( p < 0.001). Emotional reactivity appears to be a relevant dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms. Levels of high-sensitivity C-reactive protein may be an objective marker of emotional dysregulation in BD. Further studies are needed to confirm our findings.

Emotional reactivity, functioning and chronic inflammation in remitted bipolar patients: Clinical relevance of a dimensional approach

Aims To examine emotional reactivity (ER) as a dimension that may contribute to the better characterization of subsyndromal mood symptoms in bipolar disorder (BD) patients during remission, and to explore the association between ER, psychosocial functioning and levels of C-reactive protein (CRP, a biomarker of low-grade inflammation) including as to whether CRP is a biosignature of ER in BD. Method Six hundred and thirteen adult BD outpatients. Assessments: psychosocial functioning by Functional Assessment Short Test (FAST),mood by Multidimensional Assessment of Thymic States(MAThyS). The MAThyS ER sub-score (0–40) characterized 3 patients: – – 16–24: normal emotional reactivity (NormalER); – >24: emotional hyperreactivity (HyperER). CRP was measured by using standard enzyme immunoassay. Statistical analyses were performed using SPSS v21. Results HypoER ( n =144; m =12.4±3.4), NormalER ( n =198; m =19.9±2.6); HyperER ( n =271; m =28.9±3.7). BD patients with HypoER or HyperER had significantly greater levels of residual mood symptoms than patients with NormalER ( P m =21±14.1) or HyperER (FAST m =20±11.2 presented lower functioning ( P m =2.8±2.0; P m =4.3±2.8; P m =1.4±1.4). Conclusions ER appear to impact psychosocial functioning as well as to be a pertinent dimension to discriminate subsyndromal mood states in remitted BD patients. CRP could be a biological validator of emotional reactivity in BD. Association between ER-CRP may be useful proxy to examine the relationship between specific symptom profiles and chronic inflammation, a potential biological state associated with BD. These novel findings could be clinically relevant, if tested and confirmed by future studies.

The ability of early changes in motivation to predict later antidepressant treatment response.

IntroductionBaseline values and early changes of emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception have not been studied to any extent in unipolar depression, although they could help to characterize different dimensions of illness that are harder to capture by clinicians, give new insights on how patients improve, and offer new early clinical markers for later treatment response.MethodsAbout 1,565 adult outpatients with major depressive disorder receiving agomelatine completed the clinician-rated 16-item quick inventory of depressive symptoms, Clinical Global Impression, and Multidimensional Assessment of Thymic States (MAThyS) rating scales at inclusion, Week 2 and Week 6. The MAThyS includes a 20-item self-rated visual analog scale (from inhibition [0] to activation [10], with [5] representing the usual state) leading to five a priori dimensions (emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception).ResultsAll MAThyS dimension scores increased from inclusion to Week 2 and from inclusion to Week 6 (P<0.001). Improvement was around 2 points (out of 10) for motivation, 1.5 points for psychomotor function, and 0.5 points for other dimensions. Motivation showed a trend to being more severely impaired at inclusion in future nonresponders (t=1.25, df=1,563, P=0.10). Its improvement at Week 2 was the most discriminating MAThyS dimension between future responders and nonresponders, and represents the best predictor of future response, with the highest area under the receptor operating characteristic curve (area under curve =0.616, 95% confidence interval [0.588–0.643], P<0.001). Finally, improvements in motivation correlated the most strongly with clinician-rated 16-item quick inventory of depressive symptoms improvement (r=−0.491, df=1,563, P<0.001).ConclusionMotivation had the most capacity for early improvement, the best predictive value for response, and the largest global margin of progress in depressed outpatients. Assessing the evolution of self-reported motivation over time in major depressive disorder could offer an interesting complementary approach to predict response.

An increase in joy after two weeks is more specific of later antidepressant response than a decrease in sadness

BackgroundEarly improvement in positive emotions—more than decreases in negative emotions—was highly predictive of treatment response in an ecologically valid prospective manner. This result needs replication with simpler assessments to determine whether it can be translated into clinical practice. Methods2049 adult depressed outpatients receiving agomelatine were assessed at inclusion, week 2, and week 6 using the clinician-rated Quick Inventory of Depressive Symptomatology, Sheehan Disability Scale, Clinical Global Impression scale, and Multidimensional Assessment of Thymic States (MATHYS), an auto-questionnaire rating the frequency of emotions, including sadness and joy, over the previous week. ResultsJoy and sadness had a relatively low correlation coefficient at baseline (r=−0.277), joy (r=−0.160) being less correlated with clinical severity than sadness (r=0.317). An increase in joy at week 2 had higher specificity (85.04%) and positive predictive value (70.55%) for treatment response than decreased sadness (57.92% and 66.04%, respectively), and the global capacity of the former to predict remission, either clinical (Yule Q coefficient, 39.96%) or functional (44.35%), was even better compared to the prediction of clinical response (37.38%). LimitationsMATHYS retrospectively assesses emotions, with five possible ratings only, relying on self-rated frequencies. With only a 6-week follow-up, conclusions are limited to short-term aspects of clinical and functional remission. ConclusionsEarly improvement in joy during the first 2 weeks of treatment is strongly specific for treatment response and remission. The frequency of joy captures the predictivity and may deserve further study regarding inclusion in depressive rating scales.

Inhibition/activation in bipolar disorder: validation of the Multidimensional Assessment of Thymic States scale (MAThyS)

BackgroundOne of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. In this context, the MAThyS (Multidimensional Assessment of Thymic States) scale was built to assess activation/inhibition levels in all bipolar mood episodes, and to determine whether a clinical description in terms of activation/inhibition can help better define bipolar states with which both manic and depressive symptoms are associated. The aim of this paper is the validation of the MAThyS scale in 141 bipolar patients in acute states (manic, hypomanic, mixed, or depressive).MethodsThe validation of the MAThyS scale was the primary outcome of this 24-week, phase III, open-label, olanzapine single-arm clinical trial. Principal component, factorial analysis, and Cronbach’s coefficient calculation (internal consistency) were performed. Concurrent validity (correlations with 17-item Hamilton Depression Rating Scale [HAMD-17], Hamilton Anxiety Rating Scale [HAMA], and Young Mania Rating Scale [YMRS]) and responsiveness to the clinical intervention were assessed (change in MAThyS scale and effect size) at 6 and 24 weeks.ResultsScree plot of eigenvalues identified a 2-dimension structure (“activation/inhibition level” and “emotional component”). Psychometric properties were good: Cronbach’s coefficient was >0.9. Concurrent validity was good with low correlation (−0.19) with the HAMA scale and a higher correlation at baseline with the YMRS (0.72) and HAMD-17(−0.43). As expected, the activation state was predominant in manic, hypomanic, and mixed states while inhibition was predominant in depressive states. MAThyS score improvement was observed (effect size: -0.3 at 6 and 24 weeks).ConclusionsThe MAThyS demonstrated good psychometric properties. The MAThyS scale may help clinicians to better discriminate and follow bipolar episodes, especially the broad spectrum of mixed episodes.Trial registrationClinicalTrials.gov registration identification number: NCT#002592722

From inhibition to activation, from emotional hyporeactivity to emotional hyperreactivity: Two pathways to discriminate mood in bipolar disorders

To better explore the clinical heterogeneity of bipolar mood states, we developed a dimensional scale for assessing all mood episodes (depressive, hypomanic, manic, mixed states) using the same tool. The Multidimensional Assessment of Thymic States (MATHYS) (Henry et al., 2008) provides two scores, a total score measuring a level of activation and a sub-score of emotional reactivity. The aim of this study was to establish the appropriate cut-off in total activation versus inhibition and in the emotional reactivity sub-score in bipolar disorders. Patients (n=187) during an acute episode and controls (n=89) filled in the MATHYS. Receiver Operating Characteristic (ROC) curves were obtained to estimate the sensitivity and specificity of the global score and the emotional reactivity sub-score of the MATHYS, in order to differentiate patients from controls. ROC curves showed very satisfactory sensitivity and specificity levels both for the total score and the sub-score of emotional reactivity, thus providing an appropriate cut-off. Concerning the total score between 0 and 200, patients with a score lower than 91 had significant global inhibition and those with a score higher than 109 had significant global activation. Regarding the emotional reactivity sub-score between 0 and 40, patients with a score lower than 16 had significant emotional hyporeactivity and those with a score higher than 24 had significant emotional hyperreactivity. Our results provide cut-offs for the MATHYS to identify patients in an acute phase.

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.

Evidence for Two Types of Bipolar Depression Using a Dimensional Approach

Background: Although there is a great heterogeneity of depressive states in bipolar patients, there is only one definition in international classifications for describing them. However, this variety seems particularly important to recognize because of the possible exacerbation of some of these bipolar depressive states by antidepressants. We aimed at assessing whether it is possible to distinguish different forms of bipolar depression using a dimensional approach. Methods: We characterized 60 bipolar patients with a Major Depressive Episode (DSM-IV) using a new tool (MAThyS; Multidimensional Assessment of Thymic States), assessing five fundamental dimensions (emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception) of mood states. Results: A cluster analysis using the items of the dimensional scale revealed two types of depressive state: group 1 (n = 38), which had a low score, is characterized by an inhibition in all dimensions, whereas group 2 (n = 22) is characterized by an overactivation. The emotional reactivity is the most relevant dimension for discriminating these two types of depression (group 1: hyporeactivity; group 2: hyperreactivity), whereas sadness is not. Conclusions: Bipolar depressive states are not homogeneous. A dimensional approach based on emotional reactivity could be useful for discriminating the different forms of bipolar depression. Bipolar depressions may be classified as hyporeactive or hyperreactive. This classification might have therapeutic implications, because hyperreactive depression should belong to the broad spectrum of mixed states.

Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model

Background DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. Method We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. Results This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. Conclusion A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies.

Mise en évidence de deux types de dépression bipolaire à l'aide d'une approche dimensionnelle. Implication thérapeutique

Introduction Although depressive moods are recognised as a very broad condition, there is still only one definition in international classifications for describing a major depressive episode (MDE). However, there is currently some controversy surround the treatment of depressive states. This includes SSRIs and suicide in adolescents, and more specifically in bipolar disorders where some depressions are made worse by antidepressants. New data has suggested that depressive states in BP patients can be improved by atypical antipsychotics. Aim We aimed to assess 1) whether it is possible to distinguish different forms of bipolar depression using a dimensional approach, and 2) if, yes, whether there are different patterns of treatment response. Method We characterised 60 bipolar patients with a Major Depressive Episode (DSM-IV) using a new tool (MATHYS: Multidimensional Assessment of Thymic States) assessing five fundamental dimensions (emotional reactivity, cognitive speed, psycho-motricity, motivation and senses perception) of mood states (full description elsewhere). Results A cluster analysis using the items of the dimensional scale revealed two types of depressive states. One group (G1; N = 38), which had a low score, is characterised by an inhibition in all dimensions, whereas the other group (G2; N = 22) is characterised by an over-activation. Emotional reactivity is a useful dimension for discriminating these two types of depression (G1: hyporeactivity; G2: hyperreactivity) whereas sadness is not. A lower score on the MAThyS scale at day 1 was associated with a good response to antidepressant treatment, whereas higher scores were linked to a good response to a mood stabilizers alone or in combination with an antipsychotic. Conclusion Bipolar depressive states are not homogeneous and this heterogeneity can explain various patterns of treatment response. A dimensional approach could be useful for discriminating the different forms of bipolar depression and to help manage treatment.